FI66358C - FOERFARANDE FOER FRAMSTAELLNING AV TERAPEUTISKT VERKSAMMA HYDROXIDERIVAT AV 2-ISOPROPYLAMINO-PYRIMIDIN - Google Patents
FOERFARANDE FOER FRAMSTAELLNING AV TERAPEUTISKT VERKSAMMA HYDROXIDERIVAT AV 2-ISOPROPYLAMINO-PYRIMIDIN Download PDFInfo
- Publication number
- FI66358C FI66358C FI801083A FI801083A FI66358C FI 66358 C FI66358 C FI 66358C FI 801083 A FI801083 A FI 801083A FI 801083 A FI801083 A FI 801083A FI 66358 C FI66358 C FI 66358C
- Authority
- FI
- Finland
- Prior art keywords
- isopropylamino
- hydroxiderivat
- verksamma
- pyrimidin
- terapeutiskt
- Prior art date
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
- C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
- C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (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)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
Description
----_·Ί Μ KUULUTUSjULKAISU //7CO----_ · Ί Μ ANNOUNCEMENT // 7CO
jjSSTgk ™ ^ UTLÄGGN I NGSSKIUFT 0 00D0 C ί45) P-lonU! - -ly ^ ^ ¢1) pmtXX^ C 07 D 239/46 SUOMI—Fl N LAN D (21) p*MMtih»k«mu*—ρ»*·**η·«οιΐηι 801083 ¢22) HakmntapUv· — AntOkntngtda· 03.04.80 (23) AlkuptM—GlMgkocadag 03.04.80 (41) Taltat lulUMkH — Bllvtt aHw*»t 31 .10.80 PM*rtti.J· reklaterlhallitut n*****™,]. p**.- ,Q n, ö,jjSSTgk ™ ^ UTLÄGGN I NGSSKIUFT 0 00D0 C ί45) P-lonU! - -ly ^ ^ ¢ 1) pmtXX ^ C 07 D 239/46 ENGLISH — Fl N LAN D (21) p * MMtih »k« mu * —ρ »* · ** η ·« οιΐηι 801083 ¢ 22) HakmntapUv · - AntOkntngtda · 03.04.80 (23) AlkuptM — GlMgkocadag 03.04.80 (41) Taltat lulUMkH - Bllvtt aHw * »t 31 .10.80 PM * rtti.J · reklaterlhallitut n ***** ™,]. p ** .-, Q n, ö,
Patent- och refhtarttyraltan 7 Amftkan uttagd odt utLskrtftM paMicarad 23.06.o4 (32)(33)(31) I*rr***r «*otkm»—ugud pr**** 30.04.79Patent- och refhtarttyraltan 7 Amftkan uttagd odt utLskrtftM paMicarad 23.06.o4 (32) (33) (31) I * rr *** r «* otkm» —ugud pr **** 30.04.79
Englanti-England(GB) 7914987 (71) Society d'Etudes de Produits Chimiques, 4, rue Th£odule Ribot, 75017 Paris, Ranska-Frankrike(FR) (72) Andr6 Esanu, Paris, Ranska-Frankrike(FR) (74) Leitz inger Oy (54) Menetelmä valmistaa terapeuttisesti vaikuttavia 2-isopropyyliamino--pyrimidiin in hydroksijohdannaisia - Förfarande för framstallning av terapeutiskt verksamma hydroxiderivat av 2-isopropylamino-pyrimidinEngland-England (GB) 7914987 (71) Society d'Etudes de Produits Chimiques, 4, rue Th £ odule Ribot, 75017 Paris, France-France (FR) (72) Andr6 Esanu, Paris, France-France (FR) ( 74) Leitz Inger Oy (54) Method for the preparation of therapeutically active 2-isopropylamino-pyrimidine in hydroxy derivatives - Förfarande för framstallning av therapeutiskt verksamma hydroxiderivat av 2-isopropylamino-pyrimidin
Oheisen keksinnön kohteena on menetelmä valmistaa terapeuttisesti vaikuttavia 2-isopropyyliamino-pyrimidiinin hydroksijohdannaisia, joiden kaava I on A\ W-N .CH3 —C ))—nh-ch 5 // \ CH, f— N 3 (I) A6 jossa kukin ryhmistä A4, Ag ja Ag on vetyatomi tai hydroksiryhmä, edellyttäen, että ainakin yksi ryhmistä A4, Ag ja Ag ei ole vetyatomi.The present invention relates to a process for the preparation of therapeutically active hydroxy derivatives of 2-isopropylaminopyrimidine of the formula I is A (WN. CH 3 -C)) - nh-ch 5 // CH, f-N 3 (I) A6 wherein each of the groups A4 , Ag and Ag are a hydrogen atom or a hydroxy group, provided that at least one of the groups A4, Ag and Ag is not a hydrogen atom.
Keksinnön mukaiselle menetelmälle on tunnusomaista se, että 2-isopropyyliamino-pyrimidiinin halogeenijohdannaista, jonka kaava on 2 66358 A1 n\ /ch3 (idThe process according to the invention is characterized in that the halogen derivative of 2-isopropylaminopyrimidine of the formula 2 66358 A1 n \ / ch3 (id
A,5“\_ />~NH-CHA, 5 "NH-CH
y— n ch3 A,6 jossa kukin ryhmistä A'A’g ja A'g tarkoittaa vetyatomia tai halogeeniatomia, edellyttäen, että ainakin yksi ryhmistä A'A*5 ja A'g ei ole vetyatomi ehdon ollessa sama kuin edellä, käsitellään mineraaliemäksellä vedessä 100 - 150°C:ssa kuparin läsnäollessa.y- n ch3 A, 6 wherein each of A'A'g and A'g represents a hydrogen atom or a halogen atom, provided that at least one of A'A * 5 and A'g is not a hydrogen atom under the same condition as above, is treated with a mineral base in water at 100-150 ° C in the presence of copper.
Seuraavat esimerkit havainnollistavat keksintöä lähemmin:The following examples further illustrate the invention:
Esimerkki 1: 2-isopropyyliamino 5-hydroksipyrimidiini 1 litran reaktoriin kaadettiin 80 ml vettä, 3 g natriumhydroksidia, hieman kuparijauhetta ja 4,3 g (0,02 moolia) 2-isopropyyliamino-5-bromi-pyrimidiiniä; reaktioseos pidettiin lämpötilassa 130 - 135°C 1 tunti, jolloin samalla sekoitettiin, ja sen jälkeen noin 12 tuntia 130 - 140°C:ssa, jolloin myös sekoitettiin.Example 1: 2-Isopropylamino 5-hydroxypyrimidine In a 1 liter reactor was poured 80 ml of water, 3 g of sodium hydroxide, a little copper powder and 4.3 g (0.02 mol) of 2-isopropylamino-5-bromopyrimidine; the reaction mixture was maintained at 130-135 ° C for 1 hour while stirring, and then at 130-140 ° C for about 12 hours while stirring.
Kuparin suodattamisen jälkeen reaktioseos uutettiin kaksi kertaa kloroformilla. Yhdistetyt uutteet tehtiin happameksi etikkahapolla pH-arvoon 6,5 - 7,0. Sen jälkeen liuos kyllästettiin natriumklori-dilla, jolloin tuote saostui. Tuote otettiin talteen ja pestiin vedellä ja sen jälkeen pentaanilla. Tuote otettiin dietyylieette-riin ja käsiteltiin hiilimustalla. Liuos väkevöitiin, jolloin tuote saostui. Tuote otettiin talteen ja kiteytettiin uudelleen vedestä tai isopropyyliasetaatista. Kiteet kuivattiin, jolloin saatiin 2,45 g (saanto 80 %) 2-isopropyyliamino-5-hydroksi-pyrimidiiniä. Alkuaineanalyysi vastasi odotettua empiiristä kaavaa C^H^jN^O.After filtration of copper, the reaction mixture was extracted twice with chloroform. The combined extracts were acidified with acetic acid to pH 6.5-7.0. The solution was then saturated with sodium chloride, whereupon the product precipitated. The product was collected and washed with water and then with pentane. The product was taken up in diethyl ether and treated with carbon black. The solution was concentrated to precipitate the product. The product was recovered and recrystallized from water or isopropyl acetate. The crystals were dried to give 2.45 g (80% yield) of 2-isopropylamino-5-hydroxypyrimidine. Elemental analysis corresponded to the expected empirical formula C ^ H ^ jN ^ O.
Lähtäaineena käytetty 2-isopropyyliamino-5-bromi-pyrimidiini saadaan helposti saattamalla 2-isopropyyliamino-pyrimidiini ja N-bromi-sukkinimidi reagoimaan keskenään stökiömetrisissä suhteissa etikkahapon läsnäollessa (saanto 84 %).The starting 2-isopropylamino-5-bromopyrimidine is readily obtained by reacting 2-isopropylamino-pyrimidine and N-bromo-succinimide in stoichiometric proportions in the presence of acetic acid (yield 84%).
3 663583 66358
Esimerkki 2: 2-isopropyyliamino 4-hydroksipyrimidiiniExample 2: 2-Isopropylamino 4-hydroxypyrimidine
Esimerkin 1 menetelmä toistettiin paitsi, että 2-isopropyyliamino- 4- klooripyrimidiiniä käytettiin 2-isopropyyliamino 5-bromipyrimi-diinin asemesta. Valkoisen kiteisen tuotteen, sulamispiste 140°C (Tottoli), saanto oli 77 %. Tuotteen analyysi vastaa täydellisesti kaavaa C^H^N^O. Rakenneanalyysi (UV-spektri) vahvistaa hydroksi-ryhmän aseman.The procedure of Example 1 was repeated except that 2-isopropylamino-4-chloropyrimidine was used instead of 2-isopropylamino-5-bromopyrimidine. The yield of the white crystalline product, melting point 140 ° C (Tottoli), was 77%. The analysis of the product corresponds exactly to the formula C ^ H ^ N ^ O. Structural analysis (UV spectrum) confirms the position of the hydroxy group.
Esimerkki 3: 2-isopropyyliamino 4,6-dihydroksipyrimidiiniExample 3: 2-Isopropylamino 4,6-dihydroxypyrimidine
Esimerkin 1 menetelmä toistettiin paitsi, että 2-isopropyyliamino 5- bromipyrimidiinin asemesta käytettiin 2-isopropyvliamino 4,6-diklooripyrimidiiniä. Valkoisen kiteisen tuotteen (sulamispiste 221 - 225°C (Tottoli) (hajoaa)), saanto oli 73 %. Tuotteen analyysi vastaa täydellisesti kaavaa C^H-L1N302 ,HC1. Rakenneanalyysi (UV-spektri) vahvistaa hydroksiryhmien aseman.The procedure of Example 1 was repeated except that 2-isopropylamino-4,6-dichloropyrimidine was used instead of 2-isopropylamino-5-bromopyrimidine. The yield of the white crystalline product (melting point 221-225 ° C (Tottoli) (decomposes)) was 73%. The analysis of the product corresponds exactly to the formula C 1 H-L 1 N 3 O 2, HCl. Structural analysis (UV spectrum) confirms the position of the hydroxy groups.
Toksisuustoxicity
Keksinnön mukaisten yhdisteiden akuutti toksisuus (mg/kg) määritettiin hiirillä i.p. ja per os. Tulokset on esitetty seuraavassa taulukossa: —^_Yhdiste Esim. 1 Esim. 2 Esim. 3The acute toxicity (mg / kg) of the compounds of the invention was determined in mice i.p. and per os. The results are shown in the following table: - ^ _ Compound Example 1 Example 2 Example 3
Antamistapa —-- ____ i.p. 200 240 260 per os 205 355 285Method of administration —-- ____ i.p. 200 240 260 per os 205 355 285
FarmakologiaPharmacology
Keksinnön mukaisen yhdisteen farmakologinen aktiivisuus on tutkittu vertailukokeella, jossa seurattiin täysikasvuisen urosrotan (Wistar) lonkkahermon regeneroitumista.The pharmacological activity of the compound of the invention has been studied in a comparative experiment in which the regeneration of the sciatic nerve of an adult male rat (Wistar) was monitored.
4 663584 66358
Rottien lonkkahermoa viotettiin kohdistamalla hermoon 20 minuuttia lämpöääntä -20°C:ssa. Sen jälkeen rottia hoidettiin määrätty aika i.p. vertailutuotteella tai keksinnön mukaisilla yhdisteillä. Hoidon lopussa rotat tapettiin, lonkkahermot erotettiin ja niihin kytkettiin 70 ohuen yhdensuuntaisen platinalangan (etäisyys 1 mm) joukko. Platinalankojen avulla seurattiin viotetun kohdan yläpuolelle syötettyä sähkösignaalia: Regeneroitunut pituus saadaan etäisimmästä langasta, josta signaali voidaan havaita.The sciatic nerve of rats was damaged by subjecting the nerve to heat for 20 minutes at -20 ° C. The rats were then treated for a specified time i.p. reference product or compounds of the invention. At the end of the treatment, the rats were sacrificed, the sciatic nerves were separated and connected to a set of 70 thin parallel platinum wires (distance 1 mm). Platinum wires were used to monitor the electrical signal applied above the damaged point: The regenerated length is obtained from the farthest wire from which the signal can be detected.
Kutakin testattua seosta ja kutakin hoitoaikaa kohti käytettiin 8 rotan ryhmää.For each mixture tested and each treatment time, 8 groups of rats were used.
Neljä seosta testattiin i.p.: Esimerkin 1 yhdiste, esimerkin 2 yhdiste, esimerkin 3 yhdiste, kaikki i.p. annoksella 10 mg/kg, ja vertailuyh-disteenä vitamiinien Bl (500 mg/kg), B6 (500 mg/kg) ja B12 ( 5 mg/kg) seos, jonka ammattimiehet tietävät olevan tehokkaimman seoksen tällä alalla. Kontrolleja ei hoidettu lainkaan. Kutakin kestoaikaa kohti &, 11, 14, 17 ja 21 päivää) käytettiin viisi 8 eläimen ryhmää sekä kontrolleille, yhdisteille 1, 2, 3 että vertailuseokselle.Four mixtures were tested i.p .: Example 1 compound, Example 2 compound, Example 3 compound, all i.p. at a dose of 10 mg / kg, and as a reference compound a mixture of vitamins B1 (500 mg / kg), B6 (500 mg / kg) and B12 (5 mg / kg), which are known to those skilled in the art to be the most effective mixture in this field. Controls were not performed at all. For each duration & (11, 14, 17, and 21 days), five groups of 8 animals were used for both controls, compounds 1, 2, 3, and control mixture.
Seuraavaan taulukkoon on koottu tämän kokeen tulokset ja kontrolli-eläimillä saadut arvot. Regeneroituneiden hermojen pituudet on annettu mm:ssä vastaavan päivän pystyrivissä jokaisen ryhmän kaikilla eläimillä mitattujen pituuksien keskiarvona. Kun mitään lukua ei ole esitetty (17 ja 21 päivää), tämä tarkoittaa, että regeneroitunut pituus oli suurempi kuin otetun näytteen pituus.The following table summarizes the results of this experiment and the values obtained with control animals. The lengths of the regenerated nerves are given in mm in the vertical row of the corresponding day as the average of the lengths measured in all animals in each group. When no figure is shown (17 and 21 days), this means that the regenerated length was greater than the length of the sample taken.
_ Kestoaika (päivää) 7 ^ 21_ Duration (days) 7 ^ 21
Yhdiste ja annos iTpT" ____Compound and dose iTpT "____
Kontrollit 5,1 10,2 12,8 17,8 22,4Controls 5.1 10.2 12.8 17.8 22.4
Esimerkki 1 c -> 10 mg/kg 6'6 14’1 26'3Example 1 c -> 10 mg / kg 6'6 14'1 26'3
Esimerkki 2 8 10 mg/kg 'Example 2 8 10 mg / kg '
Esimerkki 3 ^ _ 10 mg/kg 6'7 15'6 26'7 MO mg/kg'%00 mg/kg ja 5 mg/kg 8’8 13'4 15·8 20'4 23'7 __I_i _]_I_ 66358 5Example 3 ^ _ 10 mg / kg 6'7 15'6 26'7 MO mg / kg '% 00 mg / kg and 5 mg / kg 8'8 13'4 15 · 8 20'4 23'7 __I_i _] _I_ 66358 5
Valmistusmuoto-posologia Nämä johdokset voidaan valmistaa missä tahansa terapeuttisesti hyväksyttävässä muodossa, esimerkiksi tableteissa tai gelatiinikapse-leissa, jotka sisältävät johdosta 5 mg per yksikköannos apuainetta. Injisoitavaa muotoa varten tuote voidaan annostella lääkepullosiin, jotka sisältävät vähintään 1 mg aktiivista ainesosaa veteen liuotettuna hydrokloridisuolana. Annostus ihmisillä oraalisessa antamis-tavassa on 25 mg - 1 g per diem, kun taas injisoitavaa muotoa voidaan antaa annoksina välillä 1 mg - 50 mg per diem.Formulation Posology These derivatives may be prepared in any therapeutically acceptable form, for example, tablets or gelatin capsules containing 5 mg per unit dose of excipient. For injection, the product can be dispensed into vials containing at least 1 mg of active ingredient dissolved in water as the hydrochloride salt. The dosage in humans for oral administration is 25 mg to 1 g per diem, while the injectable form can be administered in doses ranging from 1 mg to 50 mg per diem.
Seuraavassa on annettu esimerkki tablettimuodosta: - Jonkin esimerkin mukainen yhdiste 5 mg - Laktoosi 70 mg - Talkki 20 mg - Magnesiumstearaatti 5 mg 100 mgThe following is an example of a tablet form: - Compound according to one example 5 mg - Lactose 70 mg - Talc 20 mg - Magnesium stearate 5 mg 100 mg
Claims (3)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7914987 | 1979-04-30 | ||
| GB7914987 | 1979-04-30 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI801083A FI801083A (en) | 1980-10-31 |
| FI66358B FI66358B (en) | 1984-06-29 |
| FI66358C true FI66358C (en) | 1984-10-10 |
Family
ID=10504858
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI801084A FI66359C (en) | 1979-04-30 | 1980-04-03 | FOERFARANDE FOER FRAMSTAELLNING AV TERAPEUTISKT VERKSAMMA HYDROXIDERIVAT AV 2-ISOPROPYLAMINO-PYRIMIDIN |
| FI801083A FI66358C (en) | 1979-04-30 | 1980-04-03 | FOERFARANDE FOER FRAMSTAELLNING AV TERAPEUTISKT VERKSAMMA HYDROXIDERIVAT AV 2-ISOPROPYLAMINO-PYRIMIDIN |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI801084A FI66359C (en) | 1979-04-30 | 1980-04-03 | FOERFARANDE FOER FRAMSTAELLNING AV TERAPEUTISKT VERKSAMMA HYDROXIDERIVAT AV 2-ISOPROPYLAMINO-PYRIMIDIN |
Country Status (26)
| Country | Link |
|---|---|
| JP (2) | JPS55145670A (en) |
| AR (2) | AR222870A1 (en) |
| AT (2) | AT380013B (en) |
| BE (2) | BE882593A (en) |
| CH (2) | CH645633A5 (en) |
| DK (2) | DK183780A (en) |
| EG (2) | EG14284A (en) |
| ES (2) | ES8103061A1 (en) |
| FI (2) | FI66359C (en) |
| FR (2) | FR2455589A1 (en) |
| GB (2) | GB2054556B (en) |
| HK (2) | HK55583A (en) |
| IE (2) | IE49591B1 (en) |
| IN (2) | IN154067B (en) |
| IT (2) | IT1141487B (en) |
| LU (2) | LU82333A1 (en) |
| MA (1) | MA18824A1 (en) |
| MX (2) | MX5878E (en) |
| MY (2) | MY8400203A (en) |
| NL (2) | NL8002272A (en) |
| NO (2) | NO154056C (en) |
| NZ (2) | NZ193421A (en) |
| OA (2) | OA06525A (en) |
| PT (2) | PT71155A (en) |
| SG (2) | SG22583G (en) |
| ZA (2) | ZA801960B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63145595U (en) * | 1987-03-13 | 1988-09-26 | ||
| JPS645795U (en) * | 1987-06-26 | 1989-01-13 | ||
| JPH01100695U (en) * | 1987-12-21 | 1989-07-06 | ||
| US5264435A (en) * | 1988-12-29 | 1993-11-23 | Mitsui Petrochemical Industries, Ltd. | Pyrimidines and their pharmaceutical acceptable salts, and their use as medicines |
| HU206337B (en) * | 1988-12-29 | 1992-10-28 | Mitsui Petrochemical Ind | Process for producing pyrimidine derivatives and pharmaceutical compositions |
-
1980
- 1980-04-02 ZA ZA00801960A patent/ZA801960B/en unknown
- 1980-04-02 ZA ZA00801958A patent/ZA801958B/en unknown
- 1980-04-02 BE BE0/200083A patent/BE882593A/en not_active IP Right Cessation
- 1980-04-02 BE BE0/200084A patent/BE882594A/en not_active IP Right Cessation
- 1980-04-03 LU LU82333A patent/LU82333A1/en unknown
- 1980-04-03 FI FI801084A patent/FI66359C/en not_active IP Right Cessation
- 1980-04-03 FI FI801083A patent/FI66358C/en not_active IP Right Cessation
- 1980-04-03 LU LU82332A patent/LU82332A1/en unknown
- 1980-04-07 IN IN254/DEL/80A patent/IN154067B/en unknown
- 1980-04-07 IN IN253/DEL/80A patent/IN154066B/en unknown
- 1980-04-08 CH CH268980A patent/CH645633A5/en not_active IP Right Cessation
- 1980-04-08 CH CH269080A patent/CH645361A5/en not_active IP Right Cessation
- 1980-04-11 NZ NZ193421A patent/NZ193421A/en unknown
- 1980-04-11 NZ NZ193422A patent/NZ193422A/en unknown
- 1980-04-15 GB GB8012349A patent/GB2054556B/en not_active Expired
- 1980-04-15 GB GB8012351A patent/GB2055801B/en not_active Expired
- 1980-04-18 NL NL8002272A patent/NL8002272A/en not_active Application Discontinuation
- 1980-04-18 NL NL8002271A patent/NL8002271A/en unknown
- 1980-04-22 IT IT21542/80A patent/IT1141487B/en active
- 1980-04-22 MA MA19019A patent/MA18824A1/en unknown
- 1980-04-22 IT IT21543/80A patent/IT1141296B/en active
- 1980-04-24 AT AT0221680A patent/AT380013B/en not_active IP Right Cessation
- 1980-04-24 AT AT0221580A patent/AT380012B/en not_active IP Right Cessation
- 1980-04-25 AR AR280811A patent/AR222870A1/en active
- 1980-04-25 AR AR280810A patent/AR222869A1/en active
- 1980-04-28 IE IE864/80A patent/IE49591B1/en unknown
- 1980-04-28 MX MX808786U patent/MX5878E/en unknown
- 1980-04-28 PT PT71155A patent/PT71155A/en unknown
- 1980-04-28 NO NO801235A patent/NO154056C/en unknown
- 1980-04-28 PT PT71154A patent/PT71154A/en unknown
- 1980-04-28 NO NO801234A patent/NO154055C/en unknown
- 1980-04-28 MX MX808783U patent/MX6514E/en unknown
- 1980-04-28 JP JP5557480A patent/JPS55145670A/en active Granted
- 1980-04-28 IE IE865/80A patent/IE49709B1/en unknown
- 1980-04-28 JP JP5557580A patent/JPS55145671A/en active Granted
- 1980-04-29 DK DK183780A patent/DK183780A/en unknown
- 1980-04-29 ES ES491000A patent/ES8103061A1/en not_active Expired
- 1980-04-29 EG EG257/80A patent/EG14284A/en active
- 1980-04-29 DK DK183880A patent/DK183880A/en unknown
- 1980-04-29 EG EG258/80A patent/EG14259A/en active
- 1980-04-29 ES ES490999A patent/ES8103060A1/en not_active Expired
- 1980-04-30 OA OA57101A patent/OA06525A/en unknown
- 1980-04-30 OA OA57103A patent/OA06527A/en unknown
- 1980-04-30 FR FR8009733A patent/FR2455589A1/en active Granted
- 1980-04-30 FR FR8009732A patent/FR2455588A1/en active Granted
-
1983
- 1983-04-28 SG SG225/83A patent/SG22583G/en unknown
- 1983-04-28 SG SG222/83A patent/SG22283G/en unknown
- 1983-11-17 HK HK555/83A patent/HK55583A/en unknown
- 1983-11-17 HK HK556/83A patent/HK55683A/en unknown
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1984
- 1984-12-30 MY MY203/84A patent/MY8400203A/en unknown
- 1984-12-30 MY MY204/84A patent/MY8400204A/en unknown
Also Published As
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: SOCIETE D'ETUDES DE PRODUITS CHIMIQUES |
