FI66359C - 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
- FI66359C FI66359C FI801084A FI801084A FI66359C FI 66359 C FI66359 C FI 66359C FI 801084 A FI801084 A FI 801084A FI 801084 A FI801084 A FI 801084A FI 66359 C FI66359 C FI 66359C
- Authority
- FI
- Finland
- Prior art keywords
- isopropylamino
- hydroxiderivat
- verksamma
- terapeutiskt
- pyrimidin
- 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
R3CT ΓβΙ m,KUUUUTUSjULKAISU //7rQR3CT ΓβΙ m, ANNOUNCEMENT // 7rQ
J&fA ^ UTLÄGGNINGSSKBIFT 66θθ9 ^ ^ pi) Kv.tlu/htCL^ C 07 D 239/46 SUOMI —FINLAND (21) Ρ·*·"**»··*··** — Patvnam6k»lfi| 80 1 084 (22) HttomtaplM—AiwBkningad·! 03.04.80 (23) AlkupUv·—GlMgMadag 03.04.80 (41) TaMut (utkbvkil— BJhrtt offandlt 10 80J & fA ^ UTLÄGGNINGSSKBIFT 66θθ9 ^ ^ pi) Kv.tlu / htCL ^ C 07 D 239/46 FINLAND —FINLAND (21) Ρ · * · "**» ·· * ·· ** - Patvnam6k »lfi | 80 1 084 ( 22) HttomtaplM — AiwBkningad ·! 03.04.80 (23) AlkupUv · —GlMgMadag 03.04.80 (41) TaMut (utkbvkil— BJhrtt offandlt 10 80
Patentti· ja rekisterihallitut /44) νινμΜρμμμ J· fcMLMkaiwn pvm.— 9Q n, R,Patents · and registries / 44) νινμΜρμμμ J · fcMLMkaiwn date— 9Q n, R,
Patent· och regltterstyralsan 7 AmBIcm uthfd oeh ucUkriften ppbllcarad 29. Ob. Ö4 (32)(33)(31) Pyr>«tty «iiolkmi» ln«rd prtorteM 3 0.04.79Patent · och regltterstyralsan 7 AmBIcm uthfd oeh ucUkriften ppbllcarad 29. Ob. Ö4 (32) (33) (31) Pyr> «tty« iiolkmi »ln« rd prtorteM 3 0.04.79
Englanti-England(GB) 7914987 (71) Society d'Etudes de Produits Chimiques, 4, rue ThSodule Ribot, 75017 Paris, Ranska-Frankrike(FR) (72) Andr€ Esanu, Paris, Ranska-Frankrike(FR) (74) Leitzi nger Oy (54) Menetelmä valmistaa terapeuttisesti vaikuttavia 2-isopropyy1iamino-pyrimidiinin hydroksijohdannais ia - Förfarande för framstä11 ning av terapeut i skt verksamma hydroxiderivat av 2-isopropylamino-pyrimidinEnglish-England (GB) 7914987 (71) Society d'Etudes de Produits Chimiques, 4, rue ThSodule Ribot, 75017 Paris, French-French (FR) (72) Andr € Esanu, Paris, French-French (FR) (74) ) Leitzi nger Oy (54) The process for the preparation of therapeutically active hydroxy derivatives of 2-isopropylamino-pyrimidine and the preparation of 2-isopropylamino-pyrimide
Oheisen keksinnön kohteena on menetelmä valmistaa terapeuttisesti vaikuttavia 2-isopropyyliamino-pvrimidiinin hydroksijohdannaisia, joiden kaava I on v r=r N ^ CH3The present invention relates to a process for the preparation of therapeutically active hydroxy derivatives of 2-isopropylaminopyrimidine of the formula I is v r = r N 2 CH 3
Ar-L /)-NH-CHAr-L /) - NH-CH
)-N ^CH3 (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.) -N 2 CH 3 (I) A6 wherein each of A4 / Ag and Ag is a hydrogen atom or a hydroxy group, provided that at least one of A4, Ag and Ag is not a hydrogen atom.
Kaavan I mukaiset yhdisteet ovat mielenkiintoisia terapeutiikassa, tarkemmin sanoen erilaisten hermotautien ja lihasdystrofioiden hoidossa.The compounds of formula I are of interest in therapy, in particular in the treatment of various neurological diseases and muscular dystrophies.
Keksinnön mukaiselle menetelmälle on tunnusomaista se, että 2 66359 2-isopropyyliamino-pyrimidiinin aralkyylioksi- tai alkyylioksi-johdannainen, jonka kaava II on A" 4 v.The process according to the invention is characterized in that the aralkyloxy or alkyloxy derivative of 2-isopropylaminopyrimidine of formula II is A "4 v.
y=r N CH3 ä"5-ί V NH-CH^ CH, (II)y = r N CH3 ä "5-ί V NH-CH 2 CH, (II)
A" ' JA "'J
A 6 jossa kukin ryhmistä A"4, A"g ja A"g tarkoittaa vetyatomia tai aralkyylioksi- tai alkyylioksiryhmää, edellyttäen, että ainakin yksi ryhmistä A"4, A"5 ja A"g ei ole vetyatomi, pelkistetään vedyllä hydrauskatalyytin, kuten esimerkiksi palladiumin läsnäollessa.A 6 wherein each of A "4, A" g and A "g represents a hydrogen atom or an aralkyloxy or alkyloxy group, provided that at least one of A" 4, A "5 and A" g is not a hydrogen atom, is reduced with hydrogen over a hydrogenation catalyst such as for example in the presence of palladium.
Keksintöä havainnollistetaan seuraavien esimerkkien avulla:The invention is illustrated by the following examples:
Esimerkki 1: 2-isopropyyliamino-5-hydroksipyrimidiini 2 litran painereaktoriin, joka oli parhaiten huuhdeltu typpivir-ralla, laitettiin 0,8 g 2-isopropyyliamino-5-bentsyylioksi-pyrimi-diiniä, 40 ml metanolia ja 80 mg palladiumkatalyyttiä. Fydraus suoritetaan 2 tunnin aikana normaalissa paineessa. Katalyytti erotettiin suodattamalla ja metanoli haihdutettiin, minkä jälkeen tuote otettiin dietyylieetteriin ja liuoksesta poistettiin liukenematon aines suodattamalla. Dietyylieetteri haihdutettiin ja tuote kiteytettiin uudelleen ensin vedestä ja sen jälkeen etyyliasetaatista. Kuivaamisen jälkeen saatiin 0,4 g (saanto 80 %) 2-isopropyyliamino- 5-hydroksi-pyrimidiiniä. Alkuaineanalyysi vastasi odotettua empiiristä kaavaa CyH^NgO. Sulamispiste 161°C (Tottoli).Example 1: 2-Isopropylamino-5-hydroxypyrimidine 0.8 g of 2-isopropylamino-5-benzyloxypyrimidine, 40 ml of methanol and 80 mg of palladium catalyst were charged to a 2-liter pressure reactor, which was best purged with a stream of nitrogen. The hydration is carried out for 2 hours at normal pressure. The catalyst was filtered off and the methanol was evaporated, after which the product was taken up in diethyl ether and the insoluble matter was removed by filtration. The diethyl ether was evaporated and the product was recrystallized first from water and then from ethyl acetate. After drying, 0.4 g (yield 80%) of 2-isopropylamino-5-hydroxypyrimidine was obtained. Elemental analysis corresponded to the expected empirical formula CyH 2 NgO. Melting point 161 ° C (Tottoli).
UV-spektri vahvistaa rakenteen.The UV spectrum confirms the structure.
Esimerkki 2: 2-isopropyyliamino-4-hydroksipyrimidiiniExample 2: 2-Isopropylamino-4-hydroxypyrimidine
Esimerkissä 1 kuvatussa menetelmässä käytettiin 2-isopropyyliamino- 5-bentsyylioksipyrimidiinin asemesta 2-isopropyyliamino 4-etoksi-pyrimidiiniä. valkoisen kiteisen tuotteen, sulamispiste 140°C (Tottoli), saanto oli 83 %. Tuotteet analyysi vastaa täydellisesti kaavaa C7H11N jO. UV-spektri vahvistaa rakenteen.In the procedure described in Example 1, 2-isopropylamino-4-ethoxypyrimidine was used instead of 2-isopropylamino-5-benzyloxypyrimidine. the yield of the white crystalline product, melting point 140 ° C (Tottoli), was 83%. The products analysis perfectly corresponds to the formula C7H11N jO. The UV spectrum confirms the structure.
6635966359
Esimerkki 3: 2-isopropyyliamino-4,6-dihydroksipyrimidiini 3Example 3: 2-Isopropylamino-4,6-dihydroxypyrimidine 3
Esimerkissä 1 kuvatussa menetelmässä käytettiin 2-isopropyyliamino 5-bentsyylioksipyrimidiinin asemesta 2-isopropyyliamino 4,6-dibentsyy-lioksipyrimidiiniä. Valkoisen kiteisen tuotteen (hydrokloridi) sulamispiste 218 - 221°C (Tottoli) (hajoaa) saanto oli 78 %. Tuotteen analyysi vastaa täydellisesti kaavaa C^H^N^O , HC1· UV-spektri vahvistaa rakenteen.In the procedure described in Example 1, 2-isopropylamino-4,6-dibenzyloxypyrimidine was used instead of 2-isopropylamino-5-benzyloxypyrimidine. The white crystalline product (hydrochloride) had a melting point of 218-221 ° C (Tottoli) (decomposes) and the yield was 78%. The analysis of the product corresponds exactly to the formula C 1 H 2 N 2 O, HCl · UV spectrum confirms the structure.
Toksisuustoxicity
Keksinnön mukaisten yhdisteiden akuutti toksisuus (mg/kg) määritettiin hiirillä i.p. ja per os. Tulokset on esitetty seuraavassa taulukossa: ^'"''^'^^Yhd is te , . . 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 1Example 2Example 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 tutkittiin vertailukokeessa, jossa seurattiin täysikasvuisen urosrotan (Wistar) lonkkahermon regeneroitumista.The pharmacological activity of the compound of the invention was examined in a comparative experiment monitoring the sciatic nerve regeneration of an adult male rat (Wistar).
Rottien lonkkahermoa viotettiin kohdistamalla hermoon 20 minuuttia lämpöääntä -20°C:ssa. Sen jälkeen rottia hoidettiin määrätty aika i.p. vertailutuottee11a tai keksinnön mukaisilla yhdisteillä. Hoidon lopussa rotat tapettiin, lonkkahermot erotettiin ja niihin kytkettiin 70 ohuen yhdensuuntaisen platinalangan (etäisyys 1 mm) joukko. Platina-lankojen 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.
4 663594 66359
Neljä seosta testattiin i.p.: Esimerkin 1 yhdiste, esimerkin 2 yhdiste, esimerkin 3 yhdiste, kaikki i.p. annoksella 10 mg/kg, ja vertailuyhdis-teenä 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 (7, 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 is 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 (7, 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. Regenroituneiden 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.
’ '--KeStoaJJjaJpäivSä) Π “ 14 17 21“'- DESTINATION AND DAY) Π“ 14 17 21
Yhdiste ja annos i7pT~~~~———-_____Compound and dose i7pT ~~~~ ———-_____
Kontrollit 5,1 10,2 12,8 17,8 22,4Controls 5.1 10.2 12.8 17.8 22.4
Esimerkki 1 , c 0 10 mg/kg 6'6 14,1 26,3Example 1, c 0 10 mg / kg 6'6 14.1 26.3
Esimerkki 2 , Q Ί . . .Example 2, Q Ί. . .
10 mg/kg 14,4 26,110 mg / kg 14.4 26.1
Esimerkki 3 10 mg/kg 6,7 15,6 25,7Example 3 10 mg / kg 6.7 15.6 25.7
Bl, B6, B12 500 mg/kg, 500 mg/kg ja 5 mg/kg 8,8 13,4 15,8 20,4 23,7B1, B6, B12 500 mg / kg, 500 mg / kg and 5 mg / kg 8.8 13.4 15.8 20.4 23.7
Valmistusmuoto-posologia Nämä johdokset voidaan valmistaa missä tahansa terapeuttisesti hyväksyttävässä muodossa, esimerkiksi tableteissa tai gelatiinikapse-leissa, jotka sisältävät johdosta 5 mg per yksikköannos ja apuainetta. Injisoitavaa muotoa varten tuote voidaan annostella lääkepullosiin, jotka sisältävät vähintään 1 mg aktiivista ainesosaa veteen liuotettuna hydrokloridisuolana. Annostus ihmisillä oraalisessa antamistavassa 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 of the derivative per unit dose and 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.
5 663595 66359
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 (1)
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 |
|---|---|
| FI801084A FI801084A (en) | 1980-10-31 |
| FI66359B FI66359B (en) | 1984-06-29 |
| FI66359C true FI66359C (en) | 1984-10-10 |
Family
ID=10504858
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI801083A FI66358C (en) | 1979-04-30 | 1980-04-03 | FOERFARANDE FOER FRAMSTAELLNING AV TERAPEUTISKT VERKSAMMA HYDROXIDERIVAT AV 2-ISOPROPYLAMINO-PYRIMIDIN |
| FI801084A FI66359C (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 |
|---|---|---|---|
| FI801083A FI66358C (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) | AT380012B (en) |
| BE (2) | BE882593A (en) |
| CH (2) | CH645633A5 (en) |
| DK (2) | DK183780A (en) |
| EG (2) | EG14259A (en) |
| ES (2) | ES8103061A1 (en) |
| FI (2) | FI66358C (en) |
| FR (2) | FR2455588A1 (en) |
| GB (2) | GB2054556B (en) |
| HK (2) | HK55583A (en) |
| IE (2) | IE49709B1 (en) |
| IN (2) | IN154066B (en) |
| IT (2) | IT1141296B (en) |
| LU (2) | LU82333A1 (en) |
| MA (1) | MA18824A1 (en) |
| MX (2) | MX5878E (en) |
| MY (2) | MY8400204A (en) |
| NL (2) | NL8002271A (en) |
| NO (2) | NO154056C (en) |
| NZ (2) | NZ193421A (en) |
| OA (2) | OA06527A (en) |
| PT (2) | PT71154A (en) |
| SG (2) | SG22283G (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 BE BE0/200083A patent/BE882593A/en not_active IP Right Cessation
- 1980-04-02 ZA ZA00801960A patent/ZA801960B/en unknown
- 1980-04-02 BE BE0/200084A patent/BE882594A/en not_active IP Right Cessation
- 1980-04-02 ZA ZA00801958A patent/ZA801958B/en unknown
- 1980-04-03 LU LU82333A patent/LU82333A1/en unknown
- 1980-04-03 LU LU82332A patent/LU82332A1/en unknown
- 1980-04-03 FI FI801083A patent/FI66358C/en not_active IP Right Cessation
- 1980-04-03 FI FI801084A patent/FI66359C/en not_active IP Right Cessation
- 1980-04-07 IN IN253/DEL/80A patent/IN154066B/en unknown
- 1980-04-07 IN IN254/DEL/80A patent/IN154067B/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 NL8002271A patent/NL8002271A/en unknown
- 1980-04-18 NL NL8002272A patent/NL8002272A/en not_active Application Discontinuation
- 1980-04-22 IT IT21543/80A patent/IT1141296B/en active
- 1980-04-22 MA MA19019A patent/MA18824A1/en unknown
- 1980-04-22 IT IT21542/80A patent/IT1141487B/en active
- 1980-04-24 AT AT0221580A patent/AT380012B/en not_active IP Right Cessation
- 1980-04-24 AT AT0221680A patent/AT380013B/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 MX MX808786U patent/MX5878E/en unknown
- 1980-04-28 MX MX808783U patent/MX6514E/en unknown
- 1980-04-28 JP JP5557480A patent/JPS55145670A/en active Granted
- 1980-04-28 PT PT71154A patent/PT71154A/en unknown
- 1980-04-28 IE IE865/80A patent/IE49709B1/en unknown
- 1980-04-28 IE IE864/80A patent/IE49591B1/en unknown
- 1980-04-28 JP JP5557580A patent/JPS55145671A/en active Granted
- 1980-04-28 PT PT71155A patent/PT71155A/en unknown
- 1980-04-28 NO NO801235A patent/NO154056C/en unknown
- 1980-04-28 NO NO801234A patent/NO154055C/en unknown
- 1980-04-29 ES ES491000A patent/ES8103061A1/en not_active Expired
- 1980-04-29 ES ES490999A patent/ES490999A0/en active Granted
- 1980-04-29 EG EG258/80A patent/EG14259A/en active
- 1980-04-29 EG EG257/80A patent/EG14284A/en active
- 1980-04-29 DK DK183780A patent/DK183780A/en unknown
- 1980-04-29 DK DK183880A patent/DK183880A/en unknown
- 1980-04-30 FR FR8009732A patent/FR2455588A1/en active Granted
- 1980-04-30 OA OA57103A patent/OA06527A/en unknown
- 1980-04-30 FR FR8009733A patent/FR2455589A1/en active Granted
- 1980-04-30 OA OA57101A patent/OA06525A/en unknown
-
1983
- 1983-04-28 SG SG222/83A patent/SG22283G/en unknown
- 1983-04-28 SG SG225/83A patent/SG22583G/en unknown
- 1983-11-17 HK HK555/83A patent/HK55583A/en unknown
- 1983-11-17 HK HK556/83A patent/HK55683A/en unknown
-
1984
- 1984-12-30 MY MY204/84A patent/MY8400204A/en unknown
- 1984-12-30 MY MY203/84A patent/MY8400203A/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 |