DE2847693A1 - Verfahren zur herstellung von pyrimido-(6,1-a)-isochinolin-2-onen - Google Patents
Verfahren zur herstellung von pyrimido-(6,1-a)-isochinolin-2-onenInfo
- Publication number
- DE2847693A1 DE2847693A1 DE19782847693 DE2847693A DE2847693A1 DE 2847693 A1 DE2847693 A1 DE 2847693A1 DE 19782847693 DE19782847693 DE 19782847693 DE 2847693 A DE2847693 A DE 2847693A DE 2847693 A1 DE2847693 A1 DE 2847693A1
- Authority
- DE
- Germany
- Prior art keywords
- alkyl
- formula
- compound
- alkoxy
- halogen
- 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.)
- Withdrawn
Links
- 238000004519 manufacturing process Methods 0.000 title description 5
- 238000000034 method Methods 0.000 claims abstract description 15
- 150000001875 compounds Chemical class 0.000 claims abstract description 10
- 229910052736 halogen Chemical group 0.000 claims abstract description 10
- 150000002367 halogens Chemical group 0.000 claims abstract description 9
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000001301 oxygen Substances 0.000 claims abstract description 7
- 238000002360 preparation method Methods 0.000 claims abstract description 4
- -1 methylenedioxy Chemical group 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 150000005840 aryl radicals Chemical class 0.000 claims description 4
- 229920000137 polyphosphoric acid Polymers 0.000 claims description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 150000001340 alkali metals Chemical group 0.000 claims description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 229910001502 inorganic halide Inorganic materials 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 150000003254 radicals Chemical group 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 239000012024 dehydrating agents Substances 0.000 claims description 2
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 claims description 2
- 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 3
- 150000002431 hydrogen Chemical class 0.000 claims 2
- 238000006482 condensation reaction Methods 0.000 claims 1
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims 1
- 150000007522 mineralic acids Chemical class 0.000 claims 1
- CIVQDIGHVMGTPD-UHFFFAOYSA-N pyrimido[6,1-a]isoquinolin-4-one Chemical class C1=CC=C2C=CN3C(=O)N=CC=C3C2=C1 CIVQDIGHVMGTPD-UHFFFAOYSA-N 0.000 abstract description 8
- 229910052717 sulfur Inorganic materials 0.000 abstract description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract description 4
- 239000000543 intermediate Substances 0.000 abstract description 4
- 239000011593 sulfur Chemical group 0.000 abstract description 4
- 239000000460 chlorine Substances 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 150000007656 barbituric acids Chemical class 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- XADOJCGJGFXLAH-UHFFFAOYSA-N 1-[2-(3,4-dimethoxyphenyl)ethyl]-1,3-diazinane-2,4,6-trione Chemical compound C1=C(OC)C(OC)=CC=C1CCN1C(=O)NC(=O)CC1=O XADOJCGJGFXLAH-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- PVKCAQKXTLCSBC-UHFFFAOYSA-N 1h-isoquinolin-4-one Chemical compound C1=CC=C2C(=O)C=NCC2=C1 PVKCAQKXTLCSBC-UHFFFAOYSA-N 0.000 description 1
- DNZPLHRZXUJATK-UHFFFAOYSA-N 2-sulfanylidene-5-[[5-[2-(trifluoromethyl)phenyl]furan-2-yl]methyl]-1,3-diazinane-4,6-dione Chemical compound FC(F)(F)C1=CC=CC=C1C(O1)=CC=C1CC1C(=O)NC(=S)NC1=O DNZPLHRZXUJATK-UHFFFAOYSA-N 0.000 description 1
- DZOKENUNRMDZCS-UHFFFAOYSA-N 3h-isoquinolin-4-one Chemical class C1=CC=C2C(=O)CN=CC2=C1 DZOKENUNRMDZCS-UHFFFAOYSA-N 0.000 description 1
- HETSDWRDICBRSQ-UHFFFAOYSA-N 3h-quinolin-4-one Chemical compound C1=CC=C2C(=O)CC=NC2=C1 HETSDWRDICBRSQ-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- NKBKLKAIBIJWQR-UHFFFAOYSA-N C12=CC=CC=C2C=CN2C1=CC(=O)NC2=O Chemical compound C12=CC=CC=C2C=CN2C1=CC(=O)NC2=O NKBKLKAIBIJWQR-UHFFFAOYSA-N 0.000 description 1
- ZYAUPWZSCSJSNL-UHFFFAOYSA-N C=1C(N=CN2C1C1=CC=CC=C1C=C2)=O Chemical class C=1C(N=CN2C1C1=CC=CC=C1C=C2)=O ZYAUPWZSCSJSNL-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 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 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000001769 aryl amino group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 238000009835 boiling Methods 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
- 230000003182 bronchodilatating effect Effects 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000004983 dialkoxyalkyl group Chemical group 0.000 description 1
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 description 1
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- UXKUODQYLDZXDL-UHFFFAOYSA-N fulminic acid Chemical compound [O-][N+]#C UXKUODQYLDZXDL-UHFFFAOYSA-N 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 229910052740 iodine Inorganic materials 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
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Pulmonology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Immunology (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (21)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19782847693 DE2847693A1 (de) | 1978-11-03 | 1978-11-03 | Verfahren zur herstellung von pyrimido-(6,1-a)-isochinolin-2-onen |
| ES485489A ES8102125A1 (es) | 1978-11-03 | 1979-10-29 | Procedimiento para la preparacion de derivados de pirimido-(6,1-a)-isoquinolein-4-onas |
| AT79104238T ATE21104T1 (de) | 1978-11-03 | 1979-10-31 | Pyrimido-(6,1-a)-isochinolin-4-one, neue bei ihrer herstellung verwendete zwischenprodukte, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel. |
| DE7979104238T DE2967610D1 (en) | 1978-11-03 | 1979-10-31 | Pyrimido (6,1-a) isoquinolin-4-ones, process for their preparation and their application in medicaments; intermediates and their preparation |
| EP79104238A EP0010759B1 (de) | 1978-11-03 | 1979-10-31 | Pyrimido-(6,1-a)-isochinolin-4-one, neue bei ihrer Herstellung verwendete Zwischenprodukte, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| IL58609A IL58609A0 (en) | 1978-11-03 | 1979-11-01 | Pyrimido(6,1-a)isoquinolin-4-ones new intermediates used in their preparation and processes for their manufacture |
| JP14053279A JPS5564587A (en) | 1978-11-03 | 1979-11-01 | Pyrimidoo*6*11a**isoquinolinee44one compound and its manufacture |
| NZ191994A NZ191994A (en) | 1978-11-03 | 1979-11-01 | Preparation of certain 6,7-dihydro-4h-pyrimido (6,1-a)-isoquinolin-4-ones |
| GR60383A GR74082B (enExample) | 1978-11-03 | 1979-11-01 | |
| FI842791A FI842791A0 (fi) | 1978-11-03 | 1979-11-01 | Foerfarande foer framstaellning av pyrimido/6,1-a/isokinolin-2,4-dioner. |
| FI793430A FI66865C (fi) | 1978-11-03 | 1979-11-01 | Foerfarande foer framstaellning av pyrimido(6,1-a)isokinolin-2,4-dioner |
| AU52453/79A AU538039B2 (en) | 1978-11-03 | 1979-11-02 | Pyrimido (6,1-a)isoquinolin-4-ones |
| NO793537A NO793537L (no) | 1978-11-03 | 1979-11-02 | Pyrimido-(6,1-a)-isochinolin-4-on, nye ved deres fremstilling anvendte mellomprodukter, samt fremgangsmaate til deres fremstilling |
| ZA00795888A ZA795888B (en) | 1978-11-03 | 1979-11-02 | Pyrimido(6,1-a)isoquinolin-4-ones,new intermediates used in their preparation and processes for their manufacture |
| HU79HO2195A HU181884B (en) | 1978-11-03 | 1979-11-02 | Process for preparing new pyrimido/6,1-a/isoquinolin-4-one derivatives |
| DK465879A DK465879A (da) | 1978-11-03 | 1979-11-02 | Fremgangsmaade til fremstilling af pyrimido-(6,1-a)isoquinolin-4-oner og hertil anvendelige mellemprodukter |
| CA339,089A CA1123434A (en) | 1978-11-03 | 1979-11-02 | Pyrimido (6,1-a) isoquinolin-4-ones, new intermediates used in their preparation and processes for their manufacture |
| PT70401A PT70401A (de) | 1978-11-03 | 1979-11-02 | Pyrimido-(6,1-a)-isochinolin-4-one neue bei ihrer herstellung verwendete zwischenprodukte und verfahren zu ihrer herstellung |
| PH23245A PH15281A (en) | 1978-11-03 | 1979-11-05 | Pyrimido(6,1-a)isoquinolin-4-ones |
| ES493011A ES493011A0 (es) | 1978-11-03 | 1980-07-01 | Procedimiento para la preparacion de derivados de pirimi- do-(6,1-a)-isoquinolein-4-onas |
| US06/314,994 US4400506A (en) | 1978-11-03 | 1981-10-26 | Processes for the manufacture of pyrimido[6,1-a]isoquinolinones |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19782847693 DE2847693A1 (de) | 1978-11-03 | 1978-11-03 | Verfahren zur herstellung von pyrimido-(6,1-a)-isochinolin-2-onen |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2847693A1 true DE2847693A1 (de) | 1980-05-22 |
Family
ID=6053766
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19782847693 Withdrawn DE2847693A1 (de) | 1978-11-03 | 1978-11-03 | Verfahren zur herstellung von pyrimido-(6,1-a)-isochinolin-2-onen |
| DE7979104238T Expired DE2967610D1 (en) | 1978-11-03 | 1979-10-31 | Pyrimido (6,1-a) isoquinolin-4-ones, process for their preparation and their application in medicaments; intermediates and their preparation |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE7979104238T Expired DE2967610D1 (en) | 1978-11-03 | 1979-10-31 | Pyrimido (6,1-a) isoquinolin-4-ones, process for their preparation and their application in medicaments; intermediates and their preparation |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US4400506A (enExample) |
| EP (1) | EP0010759B1 (enExample) |
| JP (1) | JPS5564587A (enExample) |
| AT (1) | ATE21104T1 (enExample) |
| AU (1) | AU538039B2 (enExample) |
| CA (1) | CA1123434A (enExample) |
| DE (2) | DE2847693A1 (enExample) |
| DK (1) | DK465879A (enExample) |
| ES (2) | ES8102125A1 (enExample) |
| FI (1) | FI66865C (enExample) |
| GR (1) | GR74082B (enExample) |
| HU (1) | HU181884B (enExample) |
| IL (1) | IL58609A0 (enExample) |
| NO (1) | NO793537L (enExample) |
| NZ (1) | NZ191994A (enExample) |
| PH (1) | PH15281A (enExample) |
| PT (1) | PT70401A (enExample) |
| ZA (1) | ZA795888B (enExample) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4400506A (en) | 1978-11-03 | 1983-08-23 | Hoechst Aktiengesellschaft | Processes for the manufacture of pyrimido[6,1-a]isoquinolinones |
| US4612376A (en) * | 1983-03-25 | 1986-09-16 | Fujisawa Pharmaceutical Co., Ltd. | Substituted-3,4-dihydro-4-(2,4,6-trimethoxyphenylimino)-2(1H)-pyrimidones useful as cardiotonic, antihypertensive, cerebrovascular vasodilator and anti-platelet agent |
| US12168011B2 (en) | 2022-02-21 | 2024-12-17 | Verona Pharma Plc | Formulation production process |
| US12251384B1 (en) | 2023-06-26 | 2025-03-18 | Verona Pharma Plc | Particulate composition |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI64370C (fi) * | 1977-05-05 | 1983-11-10 | Hoechst Ag | Foerfarande foer framstaellning av terapeutiskt anvaendbara pyimido-(6,1-a)isokinolin-2-imino-4-onderivat |
| FR2470130A2 (fr) * | 1979-11-21 | 1981-05-29 | Hoechst Ag | Derives de pyrimido (6,1-a) isoquinoleine-4-one, leur procede de preparation et leur application en therapeutique |
| DE3126837A1 (de) * | 1981-07-08 | 1983-01-27 | Hoechst Ag, 6000 Frankfurt | Triazino-(2,1-a)isochinolinderivate |
| DE3135831A1 (de) * | 1981-09-10 | 1983-04-28 | Hoechst Ag, 6230 Frankfurt | 9,10-substituierte 2-mesitylimino-3-alkyl-3,4,6,7-tetrahydro-2h-pyrimido(6,1-a)isochinolin-4-one, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
| ZW6284A1 (en) * | 1983-05-05 | 1985-10-30 | Hoffmann La Roche | Novel pyrimidone derivatives |
| DK1165558T3 (da) * | 1999-03-31 | 2004-02-09 | Vernalis Ltd | Pyrimido[6,1-a]isoquinolin-4-on-derivater |
| PL200923B1 (pl) * | 1999-08-21 | 2009-02-27 | Nycomed Gmbh | Lek zawierający inhibitor PDE w połączeniu z agonistą receptoraß₂ -adrenergicznego oraz zastosowanie połączenia roflumilastu i salmeterolu |
| TWI347845B (en) * | 2002-03-06 | 2011-09-01 | Nycomed Gmbh | Pharmaceutical compositions,combinations,and kits for the treatment of respiratory diseases and use of the same |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| WO2008151257A2 (en) | 2007-06-04 | 2008-12-11 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| ES2627848T3 (es) | 2008-06-04 | 2017-07-31 | Synergy Pharmaceuticals Inc. | Agonistas de la guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros trastornos |
| ES2624828T3 (es) | 2008-07-16 | 2017-07-17 | Synergy Pharmaceuticals Inc. | Agonistas de la guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| MX357121B (es) | 2011-03-01 | 2018-06-27 | Synergy Pharmaceuticals Inc Star | Proceso de preparacion de agonistas c de guanilato ciclasa. |
| EP2958577A2 (en) | 2013-02-25 | 2015-12-30 | Synergy Pharmaceuticals Inc. | Guanylate cyclase receptor agonists for use in colonic cleansing |
| US9708367B2 (en) | 2013-03-15 | 2017-07-18 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase and their uses |
| EP2968439A2 (en) | 2013-03-15 | 2016-01-20 | Synergy Pharmaceuticals Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| PL3004138T3 (pl) | 2013-06-05 | 2024-07-29 | Bausch Health Ireland Limited | Ultra-oczyszczeni agoniści peptydowi cyklazy guanylanowej C, sposób ich uzyskiwania i ich zastosowanie |
| CA2920856C (en) | 2013-08-09 | 2026-03-03 | Ardelyx, Inc. | Ph modulating compounds for inhibiting gastrointestinal phosphate uptake |
| GB201613054D0 (en) | 2016-07-28 | 2016-09-14 | Verona Pharma Plc | New compound and process |
| JP2022533251A (ja) | 2019-05-21 | 2022-07-21 | アルデリックス， インコーポレイテッド | 患者において血清リン酸塩を低下させるための組み合わせ |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL251051A (enExample) * | 1959-05-02 | |||
| US3081306A (en) * | 1959-11-04 | 1963-03-12 | Pfizer & Co C | 2, 4-dioxo-3-aralkylaza-9, 10-di(lower alkoxy)-1, 2, 3, 4, 6, 7-hexahydro-11b-h-benzopyridocolines |
| GB1062357A (en) * | 1965-03-23 | 1967-03-22 | Pfizer & Co C | Quinazolone derivatives |
| US3476755A (en) * | 1967-01-17 | 1969-11-04 | Edward C Taylor | 8,13-diazasteroids |
| US3594379A (en) * | 1968-09-16 | 1971-07-20 | Sandoz Ag | 2,3-dihydroimidazo(1,2-c)quinazolines |
| US3876788A (en) * | 1970-08-27 | 1975-04-08 | Burroughs Wellcome Co | Heterocyclic compounds in the treatment of inflammatory of arthritic conditions |
| DE2720085A1 (de) * | 1977-05-05 | 1978-11-16 | Hoechst Ag | Pyrimido(6,1-a)isochinolin-2-on- derivate |
| IN147624B (enExample) | 1976-12-10 | 1980-05-03 | Hoechst Pharma | |
| FI64370C (fi) * | 1977-05-05 | 1983-11-10 | Hoechst Ag | Foerfarande foer framstaellning av terapeutiskt anvaendbara pyimido-(6,1-a)isokinolin-2-imino-4-onderivat |
| DE2847693A1 (de) | 1978-11-03 | 1980-05-22 | Hoechst Ag | Verfahren zur herstellung von pyrimido-(6,1-a)-isochinolin-2-onen |
-
1978
- 1978-11-03 DE DE19782847693 patent/DE2847693A1/de not_active Withdrawn
-
1979
- 1979-10-29 ES ES485489A patent/ES8102125A1/es not_active Expired
- 1979-10-31 EP EP79104238A patent/EP0010759B1/de not_active Expired
- 1979-10-31 AT AT79104238T patent/ATE21104T1/de not_active IP Right Cessation
- 1979-10-31 DE DE7979104238T patent/DE2967610D1/de not_active Expired
- 1979-11-01 GR GR60383A patent/GR74082B/el unknown
- 1979-11-01 IL IL58609A patent/IL58609A0/xx unknown
- 1979-11-01 FI FI793430A patent/FI66865C/fi not_active IP Right Cessation
- 1979-11-01 JP JP14053279A patent/JPS5564587A/ja active Pending
- 1979-11-01 NZ NZ191994A patent/NZ191994A/xx unknown
- 1979-11-02 DK DK465879A patent/DK465879A/da not_active Application Discontinuation
- 1979-11-02 ZA ZA00795888A patent/ZA795888B/xx unknown
- 1979-11-02 PT PT70401A patent/PT70401A/pt unknown
- 1979-11-02 AU AU52453/79A patent/AU538039B2/en not_active Ceased
- 1979-11-02 HU HU79HO2195A patent/HU181884B/hu unknown
- 1979-11-02 CA CA339,089A patent/CA1123434A/en not_active Expired
- 1979-11-02 NO NO793537A patent/NO793537L/no unknown
- 1979-11-05 PH PH23245A patent/PH15281A/en unknown
-
1980
- 1980-07-01 ES ES493011A patent/ES493011A0/es active Granted
-
1981
- 1981-10-26 US US06/314,994 patent/US4400506A/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4400506A (en) | 1978-11-03 | 1983-08-23 | Hoechst Aktiengesellschaft | Processes for the manufacture of pyrimido[6,1-a]isoquinolinones |
| US4612376A (en) * | 1983-03-25 | 1986-09-16 | Fujisawa Pharmaceutical Co., Ltd. | Substituted-3,4-dihydro-4-(2,4,6-trimethoxyphenylimino)-2(1H)-pyrimidones useful as cardiotonic, antihypertensive, cerebrovascular vasodilator and anti-platelet agent |
| US4746664A (en) * | 1983-03-25 | 1988-05-24 | Fujisawa Pharmaceutical Co., Ltd. | Substituted-3,4-dihydro-4-(2,4,6-trimethoxyphenylimino)-2(1H)-pyrimidones useful as cardiotonic, antihypertensive, cerebrovascular vasodilator and anti-platelet agent |
| US12168011B2 (en) | 2022-02-21 | 2024-12-17 | Verona Pharma Plc | Formulation production process |
| US12409180B2 (en) | 2022-02-21 | 2025-09-09 | Verona Pharma Plc | Formulation production process |
| US12251384B1 (en) | 2023-06-26 | 2025-03-18 | Verona Pharma Plc | Particulate composition |
Also Published As
| Publication number | Publication date |
|---|---|
| ZA795888B (en) | 1980-10-29 |
| DK465879A (da) | 1980-05-04 |
| AU538039B2 (en) | 1984-07-26 |
| ES8103083A1 (es) | 1981-02-16 |
| US4400506A (en) | 1983-08-23 |
| NZ191994A (en) | 1982-09-07 |
| EP0010759A2 (de) | 1980-05-14 |
| ATE21104T1 (de) | 1986-08-15 |
| NO793537L (no) | 1980-05-06 |
| GR74082B (enExample) | 1984-06-06 |
| PT70401A (de) | 1979-12-01 |
| HU181884B (en) | 1983-11-28 |
| EP0010759A3 (en) | 1981-08-19 |
| ES493011A0 (es) | 1981-02-16 |
| FI793430A7 (fi) | 1980-05-04 |
| JPS5564587A (en) | 1980-05-15 |
| IL58609A0 (en) | 1980-02-29 |
| CA1123434A (en) | 1982-05-11 |
| EP0010759B1 (de) | 1986-07-30 |
| FI66865B (fi) | 1984-08-31 |
| PH15281A (en) | 1982-11-02 |
| DE2967610D1 (en) | 1986-09-04 |
| ES485489A0 (es) | 1980-12-16 |
| FI66865C (fi) | 1984-12-10 |
| ES8102125A1 (es) | 1980-12-16 |
| AU5245379A (en) | 1980-05-08 |
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