PL136561B2 - Method of obtaining new 2-methyl-3-piperidinomethyl-3,4-dihydropyrido-/2,8-d/-pyrimidin-4-none - Google Patents
Method of obtaining new 2-methyl-3-piperidinomethyl-3,4-dihydropyrido-/2,8-d/-pyrimidin-4-none Download PDFInfo
- Publication number
- PL136561B2 PL136561B2 PL24580584A PL24580584A PL136561B2 PL 136561 B2 PL136561 B2 PL 136561B2 PL 24580584 A PL24580584 A PL 24580584A PL 24580584 A PL24580584 A PL 24580584A PL 136561 B2 PL136561 B2 PL 136561B2
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- PL
- Poland
- Prior art keywords
- methyl
- pyrimidin
- piperidinomethyl
- dihydropyrido
- none
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 6
- HTPCDVLWYUXWQR-UHFFFAOYSA-N 2-aminopyridine-3-carboxamide Chemical compound NC(=O)C1=CC=CN=C1N HTPCDVLWYUXWQR-UHFFFAOYSA-N 0.000 claims description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 9
- 230000000694 effects Effects 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000001077 hypotensive effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 230000036513 peripheral conductance Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000004202 respiratory function Effects 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
Przedmiotem wynalazku jest sposób wytwarzania nowego 2-metylo-3-piperydynometylo-3,4- dihydropirydo- [2,3-d]-pirymidyn-4-onu o wzorze 1, charakteryzujacego sie dzialaniem hipotensyjnym.Wedlug wynalazku sposób wytwarzania nowego 2-metylo-3-piperydynometylo-3,4-dihydro- pirydo-[2,3-d]-pirymidyn-4-onu o wzorze 1 polega na tym, ze na 2-aminonikotynoamid dziala sie nadmiarem acetamidu w temperaturze 403-413 K i otrzymuje sie 2-metylo-3,4-dihydropiry- do-[2,3-d]-pirymidyn-4-on o wzorze 2, na który nastepnie dziala sie nadmiarem piperydyny i formaliny w temperaturze 363 K.Na podstawie stanu techniki nie mozna bylo z góry przewidziec, ze uzyska sie reakcje przebiegajaca pomiedzy reagentami uzytymi w sposobie wedlug wynalazku i ze otrzyma sie produkt w postaci wolnej zasady Mannicha o dzialaniu farmakologicznym. Zwiazek wytworzony sposobem wedlug wynalazku wykazuje w badaniach farmakologicznych dzialanie hipotensyjne.Zwiazek ten podawany szczuromjuz w dawce 10 mg/kg powoduje spadek cisnienia, który narasta z uplywem minut, osiagajac po 60 minutach od podania 60mmHg. W zakresie wplywu zwiazku na czynnosc oddechowa u szczurów, zwalniaja o okolo 40% w dawce 10 mg/kg. Zwiazek ten w sposób statystycznie znamienny w dawce 10 mg/kg znosi wzrost obwodowego oporu naczyniowego wywolanego podaniem 50mcg noradrenaliny oraz zapobiega temu wzrostowi. W badaniach nad wplywem zwiazku na izolowane odcinki jelita cienkiego królika, zwiazek wykazuje slabe dzialanie myolityczne przy stezeniu 10 • 10~3g/cm\ Toksycznoscprzyblizona zwiazku oznaczona w tescie po podaniu dootrzewnowym u myszy wynosi 400 mg/kg.Przedmiot wynalazku jest przedstawiony w przykladzie wykonania.Przyklad. Mieszanine 10g (0.072 mola) 2-aminonikotynoamidu ogrzewa sie z 5g (0,08 mola) acetamidu w temperaturze 403-413 K w czasie 4 godzin, a nastepnie schladza, odfiltro- wuje osad i przemywa acetonem, po czym przekrystalizowuje z metanolu. Otrzymuje sie 10,57 g 2-metylo-3,4-dihydropirydo- [2,3-d]-pirvmidyn-4-onu. 1 g (0,0062 mola) wytworzonego zwiazku rozpuszcza sie w 10cm3 metanolu, do roztworu wkrapla sie 2cm3 (0,071 mola) 40% formaliny2 136 561 i 2 cm3 (0,03 mola) piperydyny. Mieszanine rozpuszczalnika oddestylowuje sie, z pozostalosci wyodrebnia sie krystaliczny produkt, który przekrystalizowuje sie z metanolu. Otrzymuje sie 1,35 g, co stanowi 84,5% wydajnosci teoretycznej, 2-metylo-3-piperydynometylo-3,4-dihydropiry- do-[2,3-d]-pirymidyn-4-onu. Zwiazek ten jest bezbarwna krystaliczna substancja o temperaturze topnienia 475-476 K, rozpuszczalna w metanolu, dimetylosulfotlenku, tetrahydrofuranie, zas nierozpuszczalna w wodzie, eterze etylowym i naftowym, która nie podlega zmianom pod wply¬ wem powietrza i swiatla.Zastrzezenie patentowe Sposób wytwarzania nowego 2-metylo-3-piperydynometylo-3,4-dihydropirydo- [2,3-d]- pirymidyn-4-onu o wzorze 1, znamienny tym, ze na 2-aminonikotynoamid dziala sie nadmiarem acetamidu w temperaturze 403-413 K i otrzymuje 2-metylo-3,4-dihydropirydo-[2,3-d]-pirymidyn- 4-on o wzorze 2, na który nastepnie dziala sie nadmiarem piperydyny i formaliny w temperaturze 363 K.WZÓR 1 WZÓR 2 Pracownia Poligraficzna UP PRL. Naklad 100 cgz.Cena 100 zl PLThe subject of the invention is a process for the preparation of a novel 2-methyl-3-piperidinomethyl-3,4-dihydropyrid- [2,3-d] -pyrimidin-4-one of the formula 1, which is characterized by a hypotensive effect. -3-piperidinomethyl-3,4-dihydro-pyrido [2,3-d] -pyrimidin-4-one of the formula 1 consists in the fact that 2-aminonicotinamide is treated with an excess of acetamide at a temperature of 403-413 K and is obtained 2-methyl-3,4-dihydropyrino- [2,3-d] -pyrimidin-4-one of the formula 2, which is then treated with an excess of piperidine and formalin at 363 K. Based on the prior art, it is not possible to it was foreseen in advance that a reaction would be obtained between the reactants used in the process of the invention and that a pharmacological Mannich free base product would be obtained. The compound according to the invention shows a hypotensive effect in pharmacological tests. This compound, administered to rats at a dose of 10 mg / kg, causes a drop in blood pressure that increases with the passing of minutes, reaching 60 minutes after the administration of 60 mmHg. In terms of the effect of compounds on respiratory function in rats, they slow down by about 40% at a dose of 10 mg / kg. This compound is statistically significant at a dose of 10 mg / kg, and prevents the increase in peripheral vascular resistance caused by the administration of 50 mcg of noradrenaline. In studies on the effect of the compound on isolated sections of the small intestine of rabbits, the compound shows a weak myolytic activity at a concentration of 10 • 10-3 g / cm \ The approximate toxicity of the compound after intraperitoneal administration in mice is 400 mg / kg. The subject of the invention is presented in the embodiment example .Example. A mixture of 10 g (0.072 mol) of 2-aminonicotinamide is heated with 5 g (0.08 mol) of acetamide at 403-413 K for 4 hours, then cooled, filtered off the precipitate and washed with acetone, then recrystallized from methanol. 10.57 g of 2-methyl-3,4-dihydropyrid- [2,3-d] pyrimidin-4-one are obtained. 1 g (0.0062 mol) of the prepared compound is dissolved in 10 cm3 of methanol, 2 cm3 (0.071 mol) of 40% formalin2 136 561 and 2 cm3 (0.03 mol) of piperidine are added dropwise to the solution. The solvent mixture is distilled off, the residue gives a crystalline product which recrystallizes from methanol. 1.35 g (84.5% of theory) of 2-methyl-3-piperidinomethyl-3,4-dihydropyrino- [2,3-d] -pyrimidin-4-one are obtained. This compound is a colorless crystalline substance with a melting point of 475-476 K, soluble in methanol, dimethylsulfoxide, tetrahydrofuran, and insoluble in water, ethyl and petroleum ether, which is not subject to changes under the influence of air and light. -methyl-3-piperidinomethyl-3,4-dihydropyrid- [2,3-d] - pyrimidin-4-one of the formula 1, characterized in that the 2-aminonicotinamide is treated with an excess of acetamide at a temperature of 403-413 K and obtained 2-methyl-3,4-dihydropyrid- [2,3-d] -pyrimidin-4-one of the formula 2, which is then treated with an excess of piperidine and formalin at a temperature of 363 K. MODEL 1 FORMULA 2 Printing workshop of the Polish People's Republic of Poland. Mintage 100 cgz Price PLN 100 PL
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL24580584A PL136561B2 (en) | 1984-01-19 | 1984-01-19 | Method of obtaining new 2-methyl-3-piperidinomethyl-3,4-dihydropyrido-/2,8-d/-pyrimidin-4-none |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL24580584A PL136561B2 (en) | 1984-01-19 | 1984-01-19 | Method of obtaining new 2-methyl-3-piperidinomethyl-3,4-dihydropyrido-/2,8-d/-pyrimidin-4-none |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PL245805A2 PL245805A2 (en) | 1984-12-03 |
| PL136561B2 true PL136561B2 (en) | 1986-02-28 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL24580584A PL136561B2 (en) | 1984-01-19 | 1984-01-19 | Method of obtaining new 2-methyl-3-piperidinomethyl-3,4-dihydropyrido-/2,8-d/-pyrimidin-4-none |
Country Status (1)
| Country | Link |
|---|---|
| PL (1) | PL136561B2 (en) |
-
1984
- 1984-01-19 PL PL24580584A patent/PL136561B2/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL245805A2 (en) | 1984-12-03 |
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