CA1141379A - Geminal dihalogen derivatives of condensed pyrimidine-4-one compounds, process for their preparation and pharmaceutical compositions containing them - Google Patents
Geminal dihalogen derivatives of condensed pyrimidine-4-one compounds, process for their preparation and pharmaceutical compositions containing themInfo
- Publication number
- CA1141379A CA1141379A CA000351662A CA351662A CA1141379A CA 1141379 A CA1141379 A CA 1141379A CA 000351662 A CA000351662 A CA 000351662A CA 351662 A CA351662 A CA 351662A CA 1141379 A CA1141379 A CA 1141379A
- Authority
- CA
- Canada
- Prior art keywords
- tetrahydro
- pyrimidine
- oxo
- pyrido
- carboxylic acid
- 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 description 36
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical class O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 title abstract 2
- 239000008194 pharmaceutical composition Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 45
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 31
- 239000001257 hydrogen Substances 0.000 claims abstract description 17
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 16
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 15
- 150000002367 halogens Chemical class 0.000 claims abstract description 15
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 14
- -1 cyano, phenyl Chemical group 0.000 claims abstract description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 125000004185 ester group Chemical group 0.000 claims abstract description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 29
- 239000002253 acid Substances 0.000 claims description 23
- 239000003795 chemical substances by application Substances 0.000 claims description 19
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 16
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 13
- 230000002140 halogenating effect Effects 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 7
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- VDCLSGXZVUDARN-UHFFFAOYSA-N molecular bromine;pyridine;hydrobromide Chemical compound Br.BrBr.C1=CC=NC=C1 VDCLSGXZVUDARN-UHFFFAOYSA-N 0.000 claims description 5
- 239000007858 starting material Substances 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 239000011230 binding agent Substances 0.000 claims description 3
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 3
- CSOYDALHEQEMAK-UHFFFAOYSA-N 2h-pyrimidine-1-carboxylic acid Chemical compound OC(=O)N1CN=CC=C1 CSOYDALHEQEMAK-UHFFFAOYSA-N 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical group 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 11
- 239000000126 substance Substances 0.000 claims 9
- YWLVFQUVWLTLJA-UHFFFAOYSA-N 9,9-dibromo-6-methyl-4-oxo-7,8-dihydro-6h-pyrido[1,2-a]pyrimidine-3-carboxylic acid Chemical compound C1=C(C(O)=O)C(=O)N2C(C)CCC(Br)(Br)C2=N1 YWLVFQUVWLTLJA-UHFFFAOYSA-N 0.000 claims 6
- KOXNRJHZWXSKMF-UHFFFAOYSA-N 6-methyl-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-3-carboxylic acid Chemical compound C1=C(C(O)=O)C(=O)N2C(C)CCCC2=N1 KOXNRJHZWXSKMF-UHFFFAOYSA-N 0.000 claims 4
- SWHJKRHVNLCDSX-UHFFFAOYSA-N 9-bromo-6-methyl-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-3-carboxylic acid Chemical compound C1=C(C(O)=O)C(=O)N2C(C)CCC(Br)C2=N1 SWHJKRHVNLCDSX-UHFFFAOYSA-N 0.000 claims 3
- VVZWMBRAVLQEKQ-UHFFFAOYSA-N 9,9-dibromo-7-methyl-4-oxo-7,8-dihydro-6h-pyrido[1,2-a]pyrimidine-3-carboxylic acid Chemical compound BrC1(Br)CC(C)CN2C1=NC=C(C(O)=O)C2=O VVZWMBRAVLQEKQ-UHFFFAOYSA-N 0.000 claims 2
- VNYHORWRAFWGHB-UHFFFAOYSA-N 9,9-dibromo-8-methyl-4-oxo-7,8-dihydro-6H-pyrido[1,2-a]pyrimidine-3-carboxylic acid Chemical compound BrC1(C(CCN2C1=NC=C(C2=O)C(=O)O)C)Br VNYHORWRAFWGHB-UHFFFAOYSA-N 0.000 claims 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims 2
- 150000008282 halocarbons Chemical class 0.000 claims 2
- BCVOWNNAKDTETP-UHFFFAOYSA-N 7-methyl-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-3-carboxylic acid Chemical compound C1=C(C(O)=O)C(=O)N2CC(C)CCC2=N1 BCVOWNNAKDTETP-UHFFFAOYSA-N 0.000 claims 1
- IZZOQVSCQFJRSI-UHFFFAOYSA-N 8-methyl-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-3-carboxylic acid Chemical compound C1C(C)CCN2C1=NC=C(C(O)=O)C2=O IZZOQVSCQFJRSI-UHFFFAOYSA-N 0.000 claims 1
- QUVNGKVLPVMJEQ-UHFFFAOYSA-N 9,9-dichloro-6-methyl-4-oxo-7,8-dihydro-6h-pyrido[1,2-a]pyrimidine-3-carboxylic acid Chemical compound C1=C(C(O)=O)C(=O)N2C(C)CCC(Cl)(Cl)C2=N1 QUVNGKVLPVMJEQ-UHFFFAOYSA-N 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
- 230000000911 decarboxylating effect Effects 0.000 claims 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 claims 1
- 230000026030 halogenation Effects 0.000 claims 1
- 238000005658 halogenation reaction Methods 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 150000003949 imides Chemical class 0.000 claims 1
- 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 1
- 230000003266 anti-allergic effect Effects 0.000 abstract description 4
- 230000001088 anti-asthma Effects 0.000 abstract description 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 239000000543 intermediate Substances 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- 230000000144 pharmacologic effect Effects 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
- 238000002844 melting Methods 0.000 description 17
- 230000008018 melting Effects 0.000 description 17
- 229960001701 chloroform Drugs 0.000 description 15
- 239000000047 product Substances 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 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 7
- 229960000583 acetic acid Drugs 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- PYRZPBDTPRQYKG-UHFFFAOYSA-N cyclopentene-1-carboxylic acid Chemical compound OC(=O)C1=CCCC1 PYRZPBDTPRQYKG-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000001632 sodium acetate Substances 0.000 description 3
- 235000017281 sodium acetate Nutrition 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- PQLAYKMGZDUDLQ-UHFFFAOYSA-K aluminium bromide Chemical compound Br[Al](Br)Br PQLAYKMGZDUDLQ-UHFFFAOYSA-K 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- JGJLWPGRMCADHB-UHFFFAOYSA-N hypobromite Chemical compound Br[O-] JGJLWPGRMCADHB-UHFFFAOYSA-N 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 229960002317 succinimide Drugs 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- WJUKOGPNGRUXMG-UHFFFAOYSA-N 1,2-dibromo-1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)(Br)C(Cl)(Cl)Br WJUKOGPNGRUXMG-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- BWJHJLINOYAPEG-HOTGVXAUSA-N 8-chloro-6-[(6-chloropyridin-3-yl)methyl]-3-[(1S,2S)-2-hydroxycyclopentyl]-7-methyl-2H-1,3-benzoxazin-4-one Chemical compound ClC1=C(C(=CC=2C(N(COC=21)[C@@H]1[C@H](CCC1)O)=O)CC=1C=NC(=CC=1)Cl)C BWJHJLINOYAPEG-HOTGVXAUSA-N 0.000 description 1
- 241001535291 Analges Species 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 101100381997 Danio rerio tbc1d32 gene Proteins 0.000 description 1
- MUQNGPZZQDCDFT-JNQJZLCISA-N Halcinonide Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CCl)[C@@]1(C)C[C@@H]2O MUQNGPZZQDCDFT-JNQJZLCISA-N 0.000 description 1
- 101100381999 Mus musculus Tbc1d32 gene Proteins 0.000 description 1
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-Chlorosuccinimide Substances ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical class [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- SYKNUAWMBRIEKB-UHFFFAOYSA-N [Cl].[Br] Chemical compound [Cl].[Br] SYKNUAWMBRIEKB-UHFFFAOYSA-N 0.000 description 1
- GPWHDDKQSYOYBF-UHFFFAOYSA-N ac1l2u0q Chemical compound Br[Br-]Br GPWHDDKQSYOYBF-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium chloride Substances Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000000489 anti-atherogenic effect Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 description 1
- 239000000292 calcium oxide Substances 0.000 description 1
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- JJCFRYNCJDLXIK-UHFFFAOYSA-N cyproheptadine Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2C=CC2=CC=CC=C21 JJCFRYNCJDLXIK-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- MCWXGJITAZMZEV-UHFFFAOYSA-N dimethoate Chemical compound CNC(=O)CSP(=S)(OC)OC MCWXGJITAZMZEV-UHFFFAOYSA-N 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229940031098 ethanolamine Drugs 0.000 description 1
- SEISMQVOJUJKGE-UHFFFAOYSA-M ethyl 1,6-dimethyl-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-1-ium-3-carboxylate;methyl sulfate Chemical compound COS([O-])(=O)=O.C1CCC(C)N2C(=O)C(C(=O)OCC)=C[N+](C)=C21 SEISMQVOJUJKGE-UHFFFAOYSA-M 0.000 description 1
- 150000003947 ethylamines Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229940028332 halog Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-O hydron;pyrimidine Chemical compound C1=CN=C[NH+]=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-O 0.000 description 1
- AAUNBWYUJICUKP-UHFFFAOYSA-N hypoiodite Chemical compound I[O-] AAUNBWYUJICUKP-UHFFFAOYSA-N 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 229960000416 rimazolium Drugs 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- ZNEOHLHCKGUAEB-UHFFFAOYSA-N trimethylphenylammonium Chemical compound C[N+](C)(C)C1=CC=CC=C1 ZNEOHLHCKGUAEB-UHFFFAOYSA-N 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B62/00—Reactive dyes, i.e. dyes which form covalent bonds with the substrates or which polymerise with themselves
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU79CI1932A HU179443B (en) | 1979-05-11 | 1979-05-11 | Process for producing substituted geminal dihalogeno-derivatives of pyrido-square bracket-1,2-a-square closed-pyrimidines,pyrrolo-square bracket-1,2-a-square bracket closed-pyrimidines and pyrimido-square bracket-1,2,-a-square bracket closed-asepines |
| HUCI-1932 | 1979-05-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1141379A true CA1141379A (en) | 1983-02-15 |
Family
ID=10994747
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000351662A Expired CA1141379A (en) | 1979-05-11 | 1980-05-09 | Geminal dihalogen derivatives of condensed pyrimidine-4-one compounds, process for their preparation and pharmaceutical compositions containing them |
Country Status (24)
| Country | Link |
|---|---|
| JP (1) | JPS5615286A (cs) |
| AT (1) | AT377261B (cs) |
| BE (1) | BE883217A (cs) |
| CA (1) | CA1141379A (cs) |
| CH (1) | CH646971A5 (cs) |
| CS (1) | CS241025B2 (cs) |
| DD (1) | DD150605A5 (cs) |
| DE (1) | DE3017564A1 (cs) |
| DK (1) | DK204680A (cs) |
| ES (1) | ES491896A0 (cs) |
| FI (1) | FI68825C (cs) |
| FR (1) | FR2456101A1 (cs) |
| GB (1) | GB2051048B (cs) |
| GR (1) | GR68518B (cs) |
| HU (1) | HU179443B (cs) |
| IL (1) | IL59967A (cs) |
| IT (1) | IT1133085B (cs) |
| LU (1) | LU82437A1 (cs) |
| NL (1) | NL8002678A (cs) |
| NO (1) | NO152607C (cs) |
| PL (1) | PL124035B1 (cs) |
| PT (1) | PT71213A (cs) |
| SE (1) | SE441747B (cs) |
| SU (1) | SU1151210A3 (cs) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU178453B (en) * | 1979-05-11 | 1982-05-28 | Chinoin Gyogyszer Es Vegyeszet | Process for producing 9-hydrazino-4-oxo-6,7,8,9-tetrahydro-4h-p-pyrido-square bracket-1,2-a-square bracket closed-pyrimidine derivatives |
| US4395549A (en) | 1981-10-02 | 1983-07-26 | Chinoin Gyogyszer Es Vegyeszeti Termekek Gyara Rt. | 6-Hydrazono-pyrido[2,1-b] quinazoline-11 ones |
| ES8501397A1 (es) * | 1982-08-05 | 1984-11-16 | Erba Farmitalia | "procedimiento para preparar derivados de quinazolina" |
| US5158952A (en) * | 1988-11-07 | 1992-10-27 | Janssen Pharmaceutica N.V. | 3-[2-[4-(6-fluoro-1,2-benzisoxozol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9 tetrahydro-9-hydroxy-2-methyl-4H-pyrido [1,2-a]pyrimidin-4-one, compositions and method of use |
| UA72189C2 (uk) | 1997-11-17 | 2005-02-15 | Янссен Фармацевтика Н.В. | Фармацевтична композиція, що містить водну суспензію субмікронних ефірів 9-гідроксирисперидон жирних кислот |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT294107B (de) * | 1966-11-02 | 1971-11-10 | Chinoin Gyogyszer Es Vegyeszet | Verfahren zur Herstellung von neuen Homopyrimidazol-Derivaten sowie von deren Salzen |
| HU178496B (en) * | 1977-12-29 | 1982-05-28 | Chinoin Gyogyszer Es Vegyeszet | Process for preparing 6,7,8,9-tetrahydro-4h-pyrido/1,2-a/pyrimidine derivatives with antiallergic activity |
-
1979
- 1979-05-11 HU HU79CI1932A patent/HU179443B/hu unknown
-
1980
- 1980-05-01 IL IL59967A patent/IL59967A/xx unknown
- 1980-05-03 GR GR61852A patent/GR68518B/el unknown
- 1980-05-08 CS CS803258A patent/CS241025B2/cs unknown
- 1980-05-08 SE SE8003479A patent/SE441747B/sv not_active IP Right Cessation
- 1980-05-08 DE DE19803017564 patent/DE3017564A1/de not_active Withdrawn
- 1980-05-08 SU SU802920002A patent/SU1151210A3/ru active
- 1980-05-09 CA CA000351662A patent/CA1141379A/en not_active Expired
- 1980-05-09 AT AT0247580A patent/AT377261B/de not_active IP Right Cessation
- 1980-05-09 GB GB8015469A patent/GB2051048B/en not_active Expired
- 1980-05-09 CH CH366380A patent/CH646971A5/de not_active IP Right Cessation
- 1980-05-09 FI FI801512A patent/FI68825C/fi not_active IP Right Cessation
- 1980-05-09 NL NL8002678A patent/NL8002678A/nl not_active Application Discontinuation
- 1980-05-09 BE BE0/200550A patent/BE883217A/fr not_active IP Right Cessation
- 1980-05-09 NO NO801378A patent/NO152607C/no unknown
- 1980-05-09 IT IT67719/80A patent/IT1133085B/it active
- 1980-05-09 LU LU82437A patent/LU82437A1/fr unknown
- 1980-05-09 FR FR8010481A patent/FR2456101A1/fr active Granted
- 1980-05-09 JP JP6161680A patent/JPS5615286A/ja active Pending
- 1980-05-09 DK DK204680A patent/DK204680A/da not_active Application Discontinuation
- 1980-05-09 PT PT71213A patent/PT71213A/pt unknown
- 1980-05-10 PL PL1980224163A patent/PL124035B1/pl unknown
- 1980-05-12 DD DD80221053A patent/DD150605A5/de unknown
- 1980-05-12 ES ES491896A patent/ES491896A0/es active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| SE8003479L (sv) | 1980-11-12 |
| FR2456101B1 (cs) | 1985-04-05 |
| IL59967A (en) | 1984-05-31 |
| FI68825B (fi) | 1985-07-31 |
| JPS5615286A (en) | 1981-02-14 |
| FI801512A7 (fi) | 1980-11-12 |
| NL8002678A (nl) | 1980-11-13 |
| ES8102570A1 (es) | 1981-02-16 |
| ES491896A0 (es) | 1981-02-16 |
| FI68825C (fi) | 1985-11-11 |
| DK204680A (da) | 1980-11-12 |
| ATA247580A (de) | 1984-07-15 |
| BE883217A (fr) | 1980-09-01 |
| SU1151210A3 (ru) | 1985-04-15 |
| AT377261B (de) | 1985-02-25 |
| NO152607B (no) | 1985-07-15 |
| NO152607C (no) | 1985-10-23 |
| GR68518B (cs) | 1982-01-11 |
| PL124035B1 (en) | 1982-12-31 |
| LU82437A1 (fr) | 1980-07-31 |
| IL59967A0 (en) | 1980-07-31 |
| DD150605A5 (de) | 1981-09-09 |
| IT1133085B (it) | 1986-07-09 |
| SE441747B (sv) | 1985-11-04 |
| PT71213A (en) | 1980-06-01 |
| DE3017564A1 (de) | 1980-11-13 |
| FR2456101A1 (fr) | 1980-12-05 |
| IT8067719A0 (it) | 1980-05-09 |
| HU179443B (en) | 1982-10-28 |
| GB2051048A (en) | 1981-01-14 |
| GB2051048B (en) | 1983-01-19 |
| CH646971A5 (de) | 1984-12-28 |
| PL224163A1 (cs) | 1981-02-13 |
| CS241025B2 (en) | 1986-03-13 |
| CS325880A2 (en) | 1985-06-13 |
| NO801378L (no) | 1980-11-12 |
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| MKEX | Expiry |