NL8002682A - Werkwijze voor de bereiding van 3-gesubstitueerde terahydro-pyrrolo/1,2-a/pyrimidinen en farmaceutische preparaten die deze verbindingen bevatten, alsmede nieuwe 3-gesubstitueerde tetrahydropyrrolo/1,2-a/ pyrimidinen. - Google Patents

Werkwijze voor de bereiding van 3-gesubstitueerde terahydro-pyrrolo/1,2-a/pyrimidinen en farmaceutische preparaten die deze verbindingen bevatten, alsmede nieuwe 3-gesubstitueerde tetrahydropyrrolo/1,2-a/ pyrimidinen. Download PDF

Info

Publication number: NL8002682A
Authority: NL; Netherlands
Prior art keywords: formula; group; short chain; compound; chain alkyl
Prior art date: 1979-05-11

Application number

NL8002682A

Other languages

English (en)

Dutch (nl)

Original Assignee

Chinoin Gyogyszer Es Vegyeszet

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1979-05-11

Filing date

1980-05-09

Publication date

1980-11-13

1980-05-09 Application filed by Chinoin Gyogyszer Es Vegyeszet filed Critical Chinoin Gyogyszer Es Vegyeszet

1980-11-13 Publication of NL8002682A publication Critical patent/NL8002682A/nl

Links

150000001875 compounds Chemical class 0.000 title claims description 45
238000000034 method Methods 0.000 title claims description 21
238000002360 preparation method Methods 0.000 title claims description 8
239000000825 pharmaceutical preparation Substances 0.000 title claims description 5
150000003230 pyrimidines Chemical class 0.000 title description 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 42
125000004494 ethyl ester group Chemical group 0.000 claims description 37
125000000217 alkyl group Chemical group 0.000 claims description 24
239000000203 mixture Substances 0.000 claims description 21
150000003839 salts Chemical group 0.000 claims description 20
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 17
229910052739 hydrogen Inorganic materials 0.000 claims description 17
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 14
239000001257 hydrogen Substances 0.000 claims description 14
238000006243 chemical reaction Methods 0.000 claims description 12
AHFWKTKIRQCWCQ-UHFFFAOYSA-N 2,3-dihydro-1h-pyrrol-5-amine Chemical class NC1=CCCN1 AHFWKTKIRQCWCQ-UHFFFAOYSA-N 0.000 claims description 11
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 11
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
239000002253 acid Substances 0.000 claims description 10
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
XEVRDFDBXJMZFG-UHFFFAOYSA-N carbonyl dihydrazine Chemical group NNC(=O)NN XEVRDFDBXJMZFG-UHFFFAOYSA-N 0.000 claims description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
150000002825 nitriles Chemical class 0.000 claims description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 4
229910021529 ammonia Inorganic materials 0.000 claims description 3
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
QNLSLYKWBHYEHK-UHFFFAOYSA-N 2-(2-formylphenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1C=O QNLSLYKWBHYEHK-UHFFFAOYSA-N 0.000 claims description 2
YIFCWYUSYGFFMH-UHFFFAOYSA-N 2-(ethoxymethylidene)propanedioic acid Chemical compound CCOC=C(C(O)=O)C(O)=O YIFCWYUSYGFFMH-UHFFFAOYSA-N 0.000 claims description 2
150000001252 acrylic acid derivatives Chemical class 0.000 claims description 2
150000001408 amides Chemical class 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 claims description 2
238000007127 saponification reaction Methods 0.000 claims description 2
MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 claims 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims 2
JWDSCUIQYJUHHM-UHFFFAOYSA-N 2-ethylacetoacetic acid Chemical compound CCC(C(C)=O)C(O)=O JWDSCUIQYJUHHM-UHFFFAOYSA-N 0.000 claims 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
238000001640 fractional crystallisation Methods 0.000 claims 1
HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical class C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 claims 1
125000002560 nitrile group Chemical group 0.000 claims 1
235000019260 propionic acid Nutrition 0.000 claims 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims 1
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 39
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
239000000155 melt Substances 0.000 description 22
239000013078 crystal Substances 0.000 description 17
239000007858 starting material Substances 0.000 description 14
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 10
239000011541 reaction mixture Substances 0.000 description 10
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
-1 3-substituted tetrahydro-pyrrolo [1,2-a] pyrimidines Chemical class 0.000 description 8
238000002844 melting Methods 0.000 description 8
230000008018 melting Effects 0.000 description 8
239000003921 oil Substances 0.000 description 8
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 5
CSOYDALHEQEMAK-UHFFFAOYSA-N 2h-pyrimidine-1-carboxylic acid Chemical compound OC(=O)N1CN=CC=C1 CSOYDALHEQEMAK-UHFFFAOYSA-N 0.000 description 5
LNRTVAGIGIAARK-UHFFFAOYSA-N 4-oxo-7,8-dihydro-6h-pyrrolo[1,2-a]pyrimidine-3-carboxylic acid Chemical compound O=C1C(C(=O)O)=CN=C2CCCN21 LNRTVAGIGIAARK-UHFFFAOYSA-N 0.000 description 4
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
125000004093 cyano group Chemical group *C#N 0.000 description 4
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
229910000041 hydrogen chloride Inorganic materials 0.000 description 4
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
239000002904 solvent Substances 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
238000001816 cooling Methods 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 3
125000004185 ester group Chemical group 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
239000012452 mother liquor Substances 0.000 description 3
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
PQCNCYLRDPVQDB-UHFFFAOYSA-N 2-methyl-2,3-dihydro-1h-pyrrol-5-amine Chemical compound CC1CC=C(N)N1 PQCNCYLRDPVQDB-UHFFFAOYSA-N 0.000 description 2
AVLHVNKKTRBNFT-UHFFFAOYSA-N 2-oxo-7,8-dihydro-6h-pyrrolo[1,2-a]pyrimidine-3-carboxylic acid Chemical compound O=C1C(C(=O)O)=CN2CCCC2=N1 AVLHVNKKTRBNFT-UHFFFAOYSA-N 0.000 description 2
SVQKXZYJADNQFF-UHFFFAOYSA-N 2H-pyrimidine-1-carboxylic acid hydrochloride Chemical compound Cl.OC(=O)N1CN=CC=C1 SVQKXZYJADNQFF-UHFFFAOYSA-N 0.000 description 2
UZURIMJIPBRTBY-UHFFFAOYSA-N 3-phenyl-7,8-dihydro-6h-pyrrolo[1,2-a]pyrimidin-2-one Chemical compound O=C1N=C2CCCN2C=C1C1=CC=CC=C1 UZURIMJIPBRTBY-UHFFFAOYSA-N 0.000 description 2
NMQFTCMTACRRTL-UHFFFAOYSA-N 6-methyl-2-oxo-7,8-dihydro-6H-pyrrolo[1,2-a]pyrimidine-3-carboxylic acid Chemical compound CC1CCC=2N1C=C(C(N=2)=O)C(=O)O NMQFTCMTACRRTL-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
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 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
241000700159 Rattus Species 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
230000001476 alcoholic effect Effects 0.000 description 2
230000003257 anti-anginal effect Effects 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
230000032050 esterification Effects 0.000 description 2
238000005886 esterification reaction Methods 0.000 description 2
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
239000007788 liquid Substances 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 2
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
239000012071 phase Substances 0.000 description 2
ZSIALBZCWCLSOG-UHFFFAOYSA-N pyrimidine;hydroiodide Chemical compound I.C1=CN=CN=C1 ZSIALBZCWCLSOG-UHFFFAOYSA-N 0.000 description 2
JBDKAABFESSFMV-UHFFFAOYSA-N pyrrolo[1,2-a]pyrimidine Chemical class N1=CC=CN2C=CC=C21 JBDKAABFESSFMV-UHFFFAOYSA-N 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
239000007787 solid Substances 0.000 description 2
238000003756 stirring Methods 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
AVAQZFUVMGMHSC-SNAWJCMRSA-N (e)-2-cyano-3-ethoxyprop-2-enoic acid Chemical compound CCO\C=C(/C#N)C(O)=O AVAQZFUVMGMHSC-SNAWJCMRSA-N 0.000 description 1
BXTVWWVOUIZHNA-UHFFFAOYSA-N 2-ethyl-2,3-dihydro-1H-pyrrol-5-amine Chemical compound NC=1NC(CC1)CC BXTVWWVOUIZHNA-UHFFFAOYSA-N 0.000 description 1
VOKUMXABRRXHAR-UHFFFAOYSA-N 2-methyl-3-oxopropanoic acid Chemical compound O=CC(C)C(O)=O VOKUMXABRRXHAR-UHFFFAOYSA-N 0.000 description 1
JSTDQAGCAJCGDO-UHFFFAOYSA-N 2-oxo-7,8-dihydro-6h-pyrrolo[1,2-a]pyrimidine-3-carboxamide Chemical compound O=C1C(C(=O)N)=CN2CCCC2=N1 JSTDQAGCAJCGDO-UHFFFAOYSA-N 0.000 description 1
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
NOAAFLAUAANAQH-UHFFFAOYSA-N 4-oxo-7,8-dihydro-6h-pyrrolo[1,2-a]pyrimidine-3-carbohydrazide Chemical compound O=C1C(C(=O)NN)=CN=C2CCCN21 NOAAFLAUAANAQH-UHFFFAOYSA-N 0.000 description 1
FIIXTQKDPFFJFO-UHFFFAOYSA-N 4-oxo-7,8-dihydro-6h-pyrrolo[1,2-a]pyrimidine-3-carboxamide Chemical compound O=C1C(C(=O)N)=CN=C2CCCN21 FIIXTQKDPFFJFO-UHFFFAOYSA-N 0.000 description 1
QLPXKYBQRVRKPC-UHFFFAOYSA-N 5-methoxy-2,3-dihydro-1h-pyrrole Chemical compound COC1=CCCN1 QLPXKYBQRVRKPC-UHFFFAOYSA-N 0.000 description 1
QYGNDKJRRNVSEC-UHFFFAOYSA-N 5-methoxy-3,4-dihydro-2h-pyrrole Chemical compound COC1=NCCC1 QYGNDKJRRNVSEC-UHFFFAOYSA-N 0.000 description 1
KRYURACLPUIPBO-UHFFFAOYSA-N 7,8-Dihydro-3-methylpyrrolo[1,2-a]pyrimidin-2(6H)-one Chemical compound O=C1C(C)=CN2CCCC2=N1 KRYURACLPUIPBO-UHFFFAOYSA-N 0.000 description 1
229930008281 A03AD01 - Papaverine Natural products 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
206010052895 Coronary artery insufficiency Diseases 0.000 description 1
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
229910000564 Raney nickel Inorganic materials 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 description 1
102000002852 Vasopressins Human genes 0.000 description 1
108010004977 Vasopressins Proteins 0.000 description 1
239000011149 active material Substances 0.000 description 1
239000013543 active substance Substances 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
125000005907 alkyl ester group Chemical group 0.000 description 1
150000001350 alkyl halides Chemical group 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 1
150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
150000007514 bases Chemical class 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
229940077388 benzenesulfonate Drugs 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
239000002775 capsule Substances 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
239000006229 carbon black Substances 0.000 description 1
235000019241 carbon black Nutrition 0.000 description 1
125000005521 carbonamide group Chemical group 0.000 description 1
125000005392 carboxamide group Chemical group NC(=O)* 0.000 description 1
239000000969 carrier Substances 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
238000006477 desulfuration reaction Methods 0.000 description 1
230000023556 desulfurization Effects 0.000 description 1
150000008050 dialkyl sulfates Chemical class 0.000 description 1
WLXALCKAKGDNAT-UHFFFAOYSA-N diazoethane Chemical compound CC=[N+]=[N-] WLXALCKAKGDNAT-UHFFFAOYSA-N 0.000 description 1
LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 0.000 description 1
DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 1
229940008406 diethyl sulfate Drugs 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000008298 dragée Substances 0.000 description 1
239000003814 drug Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
150000002168 ethanoic acid esters Chemical class 0.000 description 1
HWJHWSBFPPPIPD-UHFFFAOYSA-N ethoxyethane;propan-2-one Chemical compound CC(C)=O.CCOCC HWJHWSBFPPPIPD-UHFFFAOYSA-N 0.000 description 1
OKANYBNORCUPKZ-UHFFFAOYSA-N ethyl 2-ethyl-3-oxobutanoate Chemical compound CCOC(=O)C(CC)C(C)=O OKANYBNORCUPKZ-UHFFFAOYSA-N 0.000 description 1
HNJBEVLQSNELDL-UHFFFAOYSA-N gamma-butyrolactam Natural products O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
150000008282 halocarbons Chemical class 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
239000000543 intermediate 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
150000002576 ketones Chemical class 0.000 description 1
GOIKXGFPCJOMFO-UHFFFAOYSA-N methyl sulfate;pyrimidin-1-ium Chemical compound COS([O-])(=O)=O.C1=CN=C[NH+]=C1 GOIKXGFPCJOMFO-UHFFFAOYSA-N 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
229960001789 papaverine Drugs 0.000 description 1
239000002245 particle Substances 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
229960003424 phenylacetic acid Drugs 0.000 description 1
239000003279 phenylacetic acid Substances 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
BJDYCCHRZIFCGN-UHFFFAOYSA-N pyridin-1-ium;iodide Chemical compound I.C1=CC=NC=C1 BJDYCCHRZIFCGN-UHFFFAOYSA-N 0.000 description 1
HNJBEVLQSNELDL-YZRHJBSPSA-N pyrrolidin-2-one Chemical class O=C1CC[14CH2]N1 HNJBEVLQSNELDL-YZRHJBSPSA-N 0.000 description 1
150000004944 pyrrolopyrimidines Chemical class 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical class OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 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
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000000243 solution Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000003826 tablet Substances 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
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
229960003726 vasopressin Drugs 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

- 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
- 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
- A61P9/08—Vasodilators for multiple indications
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Cardiology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Heart & Thoracic Surgery (AREA)
General Health & Medical Sciences (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

NL8002682A 1979-05-11 1980-05-09 Werkwijze voor de bereiding van 3-gesubstitueerde terahydro-pyrrolo/1,2-a/pyrimidinen en farmaceutische preparaten die deze verbindingen bevatten, alsmede nieuwe 3-gesubstitueerde tetrahydropyrrolo/1,2-a/ pyrimidinen. NL8002682A (nl)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
HU79CI1930A HU176942B (hu)	1979-05-11	1979-05-11	Sposob poluchenija 2,3- i 3,4-dvuzamehhjonnykh tetragidro-pirrolo!1,2-a!-pirimidinov
HUCI001930		1979-05-11

Publications (1)

Publication Number	Publication Date
NL8002682A true NL8002682A (nl)	1980-11-13

Family

ID=10994745

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NL8002682A NL8002682A (nl)	1979-05-11	1980-05-09	Werkwijze voor de bereiding van 3-gesubstitueerde terahydro-pyrrolo/1,2-a/pyrimidinen en farmaceutische preparaten die deze verbindingen bevatten, alsmede nieuwe 3-gesubstitueerde tetrahydropyrrolo/1,2-a/ pyrimidinen.

Country Status (27)

Country	Link
US (1)	US4367229A (no)
JP (1)	JPS565479A (no)
AR (1)	AR225308A1 (no)
AU (1)	AU539466B2 (no)
BE (1)	BE883215A (no)
CA (1)	CA1149806A (no)
CH (1)	CH649551A5 (no)
CS (1)	CS221550B2 (no)
DD (1)	DD150612A5 (no)
DE (1)	DE3017625A1 (no)
DK (1)	DK152501C (no)
ES (1)	ES8104293A1 (no)
FI (1)	FI70218C (no)
FR (1)	FR2456105A1 (no)
GB (1)	GB2049694B (no)
GR (1)	GR68516B (no)
HU (1)	HU176942B (no)
IL (1)	IL59987A (no)
IT (1)	IT1147735B (no)
LU (1)	LU82435A1 (no)
NL (1)	NL8002682A (no)
NO (1)	NO155773C (no)
PL (1)	PL123709B1 (no)
PT (1)	PT71211A (no)
SE (1)	SE437030B (no)
SU (1)	SU1048986A3 (no)
YU (1)	YU122080A (no)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4482557A (en) *	1979-05-11	1984-11-13	Chinoin Gyogyszer Es Vegyeszeti Termekek Gyara Rt.	3-Substituted-2-oxo-tetrahydro-pyrrol[1,2-a]pyrimidines having digitalis-like activity
CA1211111A (en) *	1982-02-15	1986-09-09	Isao Yanagisawa	Process for preparing novel pyrimidone compounds
US5344933A (en) *	1991-09-11	1994-09-06	Fuji Photo Film Co., Ltd.	Pyrrole ring-or condensed pyrrole ring-containing azomethine dye
EP0971924B1 (en)	1997-01-22	2002-08-21	Ciba SC Holding AG	Photoactivatable nitrogen-containing bases based on alpha-amino ketones
JP2000026465A (ja) *	1998-07-14	2000-01-25	Fuji Photo Film Co Ltd	ピロロ［１，２−ａ］ピリミジン化合物及びそれを用いた感熱記録材料
US11983498B2 (en) *	2021-03-18	2024-05-14	Augmented Intelligence Technologies, Inc.	System and methods for language processing of document sequences using a neural network

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE1803758U (de)	1959-09-03	1960-01-07	Eugen Haller	Spritz- und spanschutz -geraet.
DE1670480C2 (de) *	1966-11-02	1983-06-01	Chinoin Gyógyszer és Vegyészeti Termékek Gyára R.T., 1045 Budapest	Pyrido[1,2-a]pyrimidinderivate, Verfahren zu deren Herstellung sowie diese Verbindungen enthaltende pharmazeutische Präparate
DE1803785A1 (de) *	1968-10-18	1970-06-04	Hoechst Ag	Verfahren zur Herstellung von 1,2-disubstituierten 6-Oxo-1.4.5.6-tetrahydropyrimidinen
BE788601A (fr) *	1971-09-10	1973-03-08	Takeda Chemical Industries Ltd	Procede de preparation de derives de pyrimidine
HU167676B (no)	1972-11-29	1975-11-28
US4209622A (en) *	1973-03-30	1980-06-24	Chinoin Gygyszer es Vegyeszeti Termekek Gyara Rt.	3-(Ethoxycarbonyl-methyl)-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine
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 HU79CI1930A patent/HU176942B/hu not_active IP Right Cessation
1980
- 1980-05-03 ES ES491153A patent/ES8104293A1/es not_active Expired
- 1980-05-03 GR GR61849A patent/GR68516B/el unknown
- 1980-05-04 IL IL59987A patent/IL59987A/xx unknown
- 1980-05-06 CS CS803171A patent/CS221550B2/cs unknown
- 1980-05-08 PL PL1980224124A patent/PL123709B1/pl unknown
- 1980-05-08 SU SU802919651A patent/SU1048986A3/ru active
- 1980-05-08 YU YU01220/80A patent/YU122080A/xx unknown
- 1980-05-08 DE DE19803017625 patent/DE3017625A1/de not_active Withdrawn
- 1980-05-08 SE SE8003477A patent/SE437030B/sv not_active IP Right Cessation
- 1980-05-09 NL NL8002682A patent/NL8002682A/nl not_active Application Discontinuation
- 1980-05-09 AU AU58276/80A patent/AU539466B2/en not_active Ceased
- 1980-05-09 FR FR8010477A patent/FR2456105A1/fr active Granted
- 1980-05-09 DK DK204880A patent/DK152501C/da not_active IP Right Cessation
- 1980-05-09 LU LU82435A patent/LU82435A1/de unknown
- 1980-05-09 DD DD80220986A patent/DD150612A5/de not_active IP Right Cessation
- 1980-05-09 BE BE0/200548A patent/BE883215A/fr not_active IP Right Cessation
- 1980-05-09 NO NO801376A patent/NO155773C/no unknown
- 1980-05-09 CA CA000351663A patent/CA1149806A/en not_active Expired
- 1980-05-09 JP JP6161380A patent/JPS565479A/ja active Pending
- 1980-05-09 IT IT67738/80A patent/IT1147735B/it active
- 1980-05-09 AR AR280967A patent/AR225308A1/es active
- 1980-05-09 FI FI801515A patent/FI70218C/fi not_active IP Right Cessation
- 1980-05-09 CH CH3661/80A patent/CH649551A5/de not_active IP Right Cessation
- 1980-05-09 GB GB8015420A patent/GB2049694B/en not_active Expired
- 1980-05-09 US US06/148,239 patent/US4367229A/en not_active Expired - Lifetime
- 1980-05-09 PT PT71211A patent/PT71211A/pt unknown

Also Published As

Publication number	Publication date
PL123709B1 (en)	1982-11-30
JPS565479A (en)	1981-01-20
AU5827680A (en)	1980-11-13
DK152501B (da)	1988-03-07
AR225308A1 (es)	1982-03-15
LU82435A1 (de)	1980-07-31
CH649551A5 (de)	1985-05-31
CS221550B2 (en)	1983-04-29
NO155773C (no)	1987-05-27
NO155773B (no)	1987-02-16
BE883215A (fr)	1980-09-01
ES491153A0 (es)	1981-04-16
FI801515A7 (fi)	1980-11-12
DK204880A (da)	1980-11-12
FI70218C (fi)	1986-09-15
DE3017625A1 (de)	1980-11-20
NO801376L (no)	1980-11-12
YU122080A (en)	1983-02-28
IT1147735B (it)	1986-11-26
AU539466B2 (en)	1984-09-27
PL224124A1 (no)	1981-02-13
PT71211A (en)	1980-06-01
US4367229A (en)	1983-01-04
ES8104293A1 (es)	1981-04-16
SE437030B (sv)	1985-02-04
SU1048986A3 (ru)	1983-10-15
IT8067738A0 (it)	1980-05-09
GB2049694B (en)	1983-05-18
FR2456105A1 (fr)	1980-12-05
SE8003477L (sv)	1980-11-12
HU176942B (hu)	1981-06-28
IL59987A0 (en)	1980-07-31
GB2049694A (en)	1980-12-31
IL59987A (en)	1984-04-30
FI70218B (fi)	1986-02-28
DD150612A5 (de)	1981-09-09
GR68516B (no)	1982-01-11
CA1149806A (en)	1983-07-12
DK152501C (da)	1988-08-08
FR2456105B1 (no)	1984-08-10

Publication	Publication Date	Title
DE2539963C2 (de)	1987-01-22	Purinverbindungen, Verfahren zu ihrer Herstellung und pharmazeutische Zubereitungen, welche diese Verbindungen enthalten
DE69613211T2 (de)	2001-11-15	Aryl- und heteroaryl- purin- und pyridopyrimidin- derivate
JPS6032638B2 (ja)	1985-07-29	３−アミノピラゾロ〔３，４−ｄ〕ピリミジン誘導体
JPS63295588A (ja)	1988-12-01	生理活性物質ｋ−２５２の誘導体
CZ283281B6 (cs)	1998-02-18	Způsob přípravy v poloze 5 substituovaných pyrrolo(2,3-d)pyrimidinů
DE69122427T2 (de)	1997-03-06	Imidazonaphthyridinderivate
Ueda et al.	1964	Pyrimidines. III. A Novel Rearrangement in the Syntheses of Imidazo-or Pyrimido [1, 2-c] pyrimidines1
NL8002682A (nl)	1980-11-13	Werkwijze voor de bereiding van 3-gesubstitueerde terahydro-pyrrolo/1,2-a/pyrimidinen en farmaceutische preparaten die deze verbindingen bevatten, alsmede nieuwe 3-gesubstitueerde tetrahydropyrrolo/1,2-a/ pyrimidinen.
EP0602097B1 (de)	1996-04-24	Tricyclische thiazol- und oxazol-derivate mit antiviraler wirkung
US4404205A (en)	1983-09-13	2-Oxo-2,6,7,8,9,10 hexahydro-pyrimido[1,2-a]azepines and antianginal method of use thereof and of 4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepines
Watson	1974	Purine N-oxides. LVII. 9-Hydroxyhypoxanthine, xanthine, and guanine
Freeman et al.	1978	The synthesis and preliminary biological testing of some bicyclic guanidine derivatives
US4482557A (en)	1984-11-13	3-Substituted-2-oxo-tetrahydro-pyrrol[1,2-a]pyrimidines having digitalis-like activity
JPS62195368A (ja)	1987-08-28	５−アミノ−１ｈ−ピラゾ−ル系化合物
Muller et al.	1982	Regioselective Synthesis of 2‐oxo‐2, 8‐dihydro‐[l, 2, 4] oxadiazolo [2, 3‐a] pyrimidine‐7‐carbamates: A New Class of Antihypertensive Peripheral Vasodilators
Watson et al.	1972	Purine N-oxides. XLIII. 9-Hydroxy-8-methylhypoxanthine,-xanthine, and-guanine
US3449344A (en)	1969-06-10	4 - amino - 2 - aryl - 6 - carbamoyl - 7,8 - dihydro - 7 - oxo - 8 - pteridineacetamides and 4 - amino - 2 - aryl - 6 - carbamoyl-7,8 - dihydro - 7 - oxo - 8 - pteridineacetic acid esters
AT384221B (de)	1987-10-12	Verfahren zur herstellung von neuen 3-substituierten tetrahydro-pyrrolo(1,2-a) pyrimidin-derivaten sowie von deren saeureadditions- und quaternaeren salzen
Eldin et al.	2002	Reactions with Maleimides XI: 1 Dipolar Cycloaddition Reactions with Thiazolonylarylhydrazones: A New Route for the Synthesis of Several New Thiazolonylpyrazoles of Expected Biological Activities
AT395154B (de)	1992-10-12	Verfahren zur herstellung von neuen imidazo(1,5-a)(1,4)diazepinverbindungen
JPS58167590A (ja)	1983-10-03	置換された１Ｈ−ピラゾロ〔１．５−ａ〕ピリミジンおよびその製法
FI56379C (fi)	1980-01-10	Foerfarande foer framstaellning av nya terapeutiskt anvaendbara 6-aza-3h-1,4-benzodiazepin-2-oner och deras salter
Ryabova et al.	2001	New approach to the functionalization of δ-carboline derivatives
HU176005B (en)	1980-11-28	Process for producing new 2-bracket-1,8-naftiridine-2-yl-bracket closed-3-square bracket-bracket-alkyl-1-piperazinyl-bracket closed-carbonyloxy-square bracket closed-trifluoromethyl-isoindolinones

Legal Events

Date	Code	Title	Description
1985-01-01	A85	Still pending on 85-01-01
1987-07-01	BV	The patent application has lapsed