CH646692A5 - PYRIDYLMETHANE DERIVATIVE WITH LAXATIVE ACTIVITY, PROCESS FOR ITS PREPARATION AND PHARMACEUTICAL COMPOSITIONS THAT CONTAIN IT. - Google Patents
PYRIDYLMETHANE DERIVATIVE WITH LAXATIVE ACTIVITY, PROCESS FOR ITS PREPARATION AND PHARMACEUTICAL COMPOSITIONS THAT CONTAIN IT. Download PDFInfo
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- CH646692A5 CH646692A5 CH456780A CH456780A CH646692A5 CH 646692 A5 CH646692 A5 CH 646692A5 CH 456780 A CH456780 A CH 456780A CH 456780 A CH456780 A CH 456780A CH 646692 A5 CH646692 A5 CH 646692A5
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/10—Laxatives
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- Pyridine Compounds (AREA)
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Description
La presente invenzione ha per oggetto un composto dotato di attività lassativa, e precisamente il bis-[p-(l-etossi--etossi)fenil]-2-piridilmetano, di formula (I) The present invention relates to a compound with laxative activity, namely bis- [p- (l-ethoxy - ethoxy) phenyl] -2-pyridylmethane, of formula (I)
H_ C O-CH-O H_ C O-CH-O
5 2 I 5 2 I
CH, CH,
OT0 (I) OT0 (I)
CH, CH,
L'invenzione riguarda inoltre un procedimento per la preparazione del composto (I), caratterizzato dal fatto che si fa reagire il bis-(p-idrossifenil)-2-piridilmetano (II) con etilvinil-etere e con catalizzatori acidi, secondo lo schema qui sotto riportato: The invention also relates to a process for the preparation of compound (I), characterized in that bis- (p-hydroxyphenyl) -2-pyridylmethane (II) is reacted with ethylvinyl ether and with acid catalysts, according to the scheme shown below:
OH +Z 0 OH + Z 0
v, v,
* (I) 55 * (I) 55
dotta in presenza di piccole quantità di acido solforico concentrato. obtained in the presence of small quantities of concentrated sulfuric acid.
È opportuno operare in solventi inerti, ad esempio in etere etilico, o in tetraidrofurano, o in diossano e simili, s II procedimento secondo l'invenzione è illustrato dall'esempio che segue: It is advisable to operate in inert solvents, for example in ethyl ether, or in tetrahydrofuran, or in dioxane and the like, s The process according to the invention is illustrated by the following example:
Esempio a) bis-(p-idrossifenilj-2-piridilmetano jo 48 grammi di bis-(p-acetossifeniI)-2-piridilmetano vengono sospesi in 300 mi di metanolo; si aggiungono quindi 23 g di idrossido di sodio sciolti in 100 mi d'acqua. Si scalda a 50°C: il prodotto indisciolto passa rapidamente in soluzione. Si lascia raffreddare a temperatura ambiente, si eva-i5 pora il metanolo sotto vuoto, si aggiungono 200 mi di acqua e quindi 103 mi di acido cloridrico 5-normale. Si raffredda a 0°C e si filtra. Si ottengono in tal modo 35 g di bis-(p--idrossifenil)-2-piridilmetano (II). Example a) bis- (p-hydroxyphenyl-2-pyridylmethane jo 48 grams of bis- (p-acetoxypheneI) -2-pyridylmethane are suspended in 300 ml of methanol; 23 g of sodium hydroxide dissolved in 100 ml are then added water is heated to 50 ° C: the undissolved product passes rapidly into solution, is left to cool to room temperature, the methanol is evaporated under vacuum, 200 ml of water are added and then 103 ml of hydrochloric acid 5- normal, the mixture is cooled to 0 ° C and filtered, thus obtaining 35 g of bis- (p - hydroxyphenyl) -2-pyridylmethane (II).
20 b) bis-[p-(l-etossi-etossi)fenil]-2-piridilmetano 20 b) bis- [p- (1-ethoxy-ethoxy) phenyl] -2-pyridylmethane
14 grammi del diidrossiderivato (II) vengono sospesi in 100 mi di tetraidrofurano. Si aggiungono 40 mi di etivinilete-re, e una goccia di acido solforico concentrato. Si tiene sotto agitazione per un'ora a temperatura ambiente, quindi si la-25 scia a sè, sempre a temperatura ambiente, per 24 ore. Dopo tale termine tutto l'indisciolto è passato in soluzione. 14 grams of the dihydroxy derivative (II) are suspended in 100 ml of tetrahydrofuran. 40 ml of etivinylether are added, and a drop of concentrated sulfuric acid. It is kept under stirring for one hour at room temperature, then it is left to stand, always at room temperature, for 24 hours. After this term all the undissolved went into solution.
Si evapora il solvente a pressione ridotta, si riprende con 250 mi d'acqua contenente 2 g di idrossido di sodio e si estrae in etere etilico. Dopo essiccamento della soluzione 30 eterea si evapora il solvente, e il resìduo ottenuto (20 g) The solvent is evaporated under reduced pressure, taken up with 250 ml of water containing 2 g of sodium hydroxide and extracted in ethyl ether. After drying the ethereal solution 30, the solvent is evaporated, and the residue obtained (20 g)
viene purificato per triplice cromatografia su allumina basica, impiegando come eluente etere di petrolio. it is purified by triple chromatography on basic alumina, using petroleum ether as eluent.
Si ottengono in tal modo 12 g di un olio denso, indistilla-bile senza decomposizione, che risulta perfettamente unitario 35 in cromatografia su strato sottile. In this way 12 g of a dense oil, indistillable without decomposition, which is perfectly unitary 35 in thin layer chromatography are obtained.
Analisi per: C26H31N04 Analysis for: C26H31N04
cale. % C 74,11 H 7,36 N 3,32 trov. % C 74,34 H 7,31 N 3,38 creeks. % C 74.11 H 7.36 N 3.32 found % C 74.34 H 7.31 N 3.38
I dati spettroscopici (IR, NMR) confermano la struttura 40 del composto in oggetto. The spectroscopic data (IR, NMR) confirm the structure 40 of the compound in question.
Le proprietà tossicologiche e farmaceutiche del composto (II), che verrà d'ora in poi definito con la sigla «Mepi-lax», sono riportate qui di seguito. The toxicological and pharmaceutical properties of compound (II), which will henceforth be defined with the abbreviation "Mepi-lax", are shown below.
45 Tossicità acuta 45 Acute toxicity
La tossicità acuta nel Mepilax è stata indagata nel topo e nel ratto per via orale e sottocutanea. Acute toxicity in Mepilax has been investigated in the mouse and rat orally and subcutaneously.
Sono stati utilizzati: topi di ceppo Sprague-Dawley di peso medio di 25 ± 10 di sesso maschile; ratti albini di ceppo so Wistar del peso medio di 120 ± 10 di sesso maschile. The following were used: Sprague-Dawley mice with an average weight of 25 ± 10 male; albino rats of the So Wistar strain with an average weight of 120 ± 10 male.
II composto in esame è stato somministrato per os mediante sondaggio gastrico solubilizzato in glicole propilenico, e per via sottocutanea sempre solubilizzato in glicole propilenico. The test compound was administered orally by gastric probing solubilized in propylene glycol, and subcutaneously always solubilized in propylene glycol.
Nelle 24 ore successive alla somministrazione fino alla In the 24 hours following administration until
(II) (II)
"CH=CH„ "CH = CH"
a sua volta, il bis-(p-idrossifenil)-2-piridilmetano è facilmente accessibile, per esempio, mediante idrolisi del corrispondente diacetossiderivato, che è un noto prodotto commerciale. La reazione tra il composto (II) e l'etilviniletere viene di preferenza effettuata a temperature comprese tra 0 e 60°C, opportunamente tra 10 e 30°C. in turn, bis- (p-hydroxyphenyl) -2-pyridylmethane is easily accessible, for example, by hydrolysis of the corresponding diacethoxy derivative, which is a known commercial product. The reaction between the compound (II) and the ethylvinylether is preferably carried out at temperatures ranging from 0 to 60 ° C, suitably between 10 and 30 ° C.
In qualità di catalizzatore si può impiegare un qualsiasi acido inorganico (solforico, fosforico, cloridrico ecc.), oppure un acido solfonico organico, o anche una resina a carattere spiccatamente acido. Di preferenza, la reazione viene condose di 3000 mg di principio attivo per os, tanto nel ratto come nel topo, non si è verificato alcun caso di morte e non si è manifestato alcun disturbo, nè nelle 24 ore, nè successivamente, ad eccezione di un marcato effetto di tipo diar-60 roico, limitatamente alle condizioni di somministrazione per os. As a catalyst, any inorganic acid (sulfuric, phosphoric, hydrochloric, etc.), or an organic sulfonic acid, or even a distinctly acidic resin can be used. Preferably, the reaction is conductive of 3000 mg of active ingredient per os, in the rat as well as in the mouse, no case of death occurred and no disturbance occurred, neither in the 24 hours, nor subsequently, with the exception of a marked diarrheal effect, limited to the oral administration conditions.
Attività lassativa Laxative activity
1) L'attività lassativa del Mepilax è stata determinata 65 utilizzando la metodica di Lish e coli. (1958) valutando la progressione dell'intestino di una sospensione di carbone vegetale per determinare eventuali effetti di stimolo o di inibizione sulla motilità intestinale. 1) The laxative activity of Mepilax was determined 65 using the Lish and coli method. (1958) evaluating the progression of the intestine of a suspension of vegetable charcoal to determine any stimulating or inhibiting effects on intestinal motility.
3 3
646 692 646 692
Materiali e metodi Materials and methods
Ratti albini maschi di ceppo Wistar del peso corporeo di circa 100 g, tenuti a digiuno da almeno 18 ore, con solo libero accesso all'acqua. Male albino rats of the Wistar strain weighing about 100 g, fasting for at least 18 hours, with only free access to water.
Prodotti utilizzati: Mepilax e, per confronto, il sale biso-dico dell'acido 4,4'-(2-picoliliden)-bis-fenilsolforico (noto come Sodium Picosulfate), entrambi in dosi di 37,5 mg/kg/os. Tempo 0 — Trattamento con i composti in esame per via orale Products used: Mepilax and, by comparison, the bisodic salt of 4,4 '- (2-picoliliden) -bis-phenylsulfuric acid (known as Sodium Picosulfate), both in doses of 37.5 mg / kg / os . Time 0 - Treatment with the test compounds orally
Dopo 3 h — Somministrazione di una sospensione di carbone vegetale al 6% in gomma arabica al 5% alla dose di 10 mi /kg After 3 h - Administration of a 6% vegetable carbon suspension in 5% arabic gum at a dose of 10 ml / kg
Dopo 3 h 45' — Uccisione animale per controllare il transito intestinale. After 3 h 45 '- Animal killing to control intestinal transit.
I risultati sono contenuti nell'allegata tabella 1. The results are contained in the attached table 1.
Dove Where is it
GX = sale bisodico dell'acido 4,4'-(2-picoliIiden)-bis-fe- GX = disodium salt of the acid 4,4 '- (2-picoliIiden) -bis-fe-
nilsolforico MX = Mepilax. nylsulphoric MX = Mepilax.
TABELLA 1 TABLE 1
Azione lassativa di GX e MX secondo il test di Lish e coli. GX and MX laxative action according to the Lish and coli test.
Prodotto Product
Animali n. Animals n.
Dose mg/kg per os Dose mg / kg per os
Variazione media percentuale di migrazione percorsa dal carbone in 45' rispetto alla distanza piloro-cieco Average percentage change in migration traveled by coal in 45 'with respect to the pylorus-blind distance
Controlli Controls
10 10
37,5 37.5
69,68 ± 4,98 69.68 ± 4.98
GX GX
10 10
37,5 37.5
75,20 ± 6,41 75.20 ± 6.41
MX MX
10 10
37,5 37.5
81,3 ± 6,25 81.3 ± 6.25
2. L'attività lassativa del Mepilax è stata inoltre determinata con la metodica di Schmidt e coli. (1962) determinando, dopo somministrazione orale di Mepilax, la percentuale di animali diarroici. 2. The laxative activity of Mepilax was also determined with the Schmidt and coli method. (1962) determining, after oral administration of Mepilax, the percentage of diarrheal animals.
Materiale e metodi Material and methods
Ratti albini femmine di ceppi Wistar, del peso corporeo di circa 70-80 g, tenuti a digiuno da circa 18 ore, con solo libero accesso all'acqua. Female albino rats of Wistar strains, of a body weight of about 70-80 g, fasted for about 18 hours, with only free access to water.
Prodotti utilizzati: Mepilax e sale bisodico dell'acido 4,4'-(2-picoliliden)-bis-fenilsolforico, omogeneizzati in gomma arabica al 5 % e somministrati in quantità di 5 ml/kg, dove equivalente a 37,5 mg/kg/os. Products used: Mepilax and disodium salt of 4,4 '- (2-picoliliden) -bis-phenylsulphuric acid, homogenised in 5% arabic gum and administered in quantities of 5 ml / kg, where equivalent to 37.5 mg / kg / os.
Durante tutto l'esperimento gli animali venivano mantenuti in gabbie singole con fondo grigliato, al di sotto del quale veniva sistemata della carta assorbente per ben evidenziare le feci e il loro stato. During the whole experiment, the animals were kept in single cages with a grilled bottom, under which absorbent paper was placed to clearly highlight the feces and their state.
La carta veniva cambiata ad ogni rilevamento. The card was changed with each detection.
I controlli effettuati nel tempo, per visionare lo stato delle feci, sono stati i seguenti: The checks carried out over time, to view the state of the stool, were the following:
Tempo 0 — Gli animali, tenuti a digiugno da circa 18 ore, sono stati trattati con i composti in esame. Dopo la somministrazione gli animali sono stati alimentati ad libitum. Time 0 - The animals, kept in the junction for about 18 hours, were treated with the compounds under examination. After administration, the animals were fed ad libitum.
Dopo 5 h — rilievo dello stato delle feci. After 5 h - survey of the state of the stool.
Dopo 7,5 h — rilievo dello stato delle feci in animali lasciati a digiuno. After 7.5 h - survey of the state of the feces in animals left on an empty stomach.
Dopo 24 h — rilievo dello stato delle feci in animali alimentati ad libitum. After 24 h - survey of the state of the feces in animals fed ad libitum.
Dopo 30 h — rilievo dello stato delle feci. After 30 h - survey of the state of the stool.
Per il rilevamento è stato indicato con un + ogni zona sulla carta con feci evidentemente diarroiche. For detection, each area on the map was marked with a + with evidently diarrheal feces.
Ogni gruppo era costituito da 10 animali, un gruppo è stato, inoltre, tenuto come controllo e trattato con solo sospendente (gomma arabica), in tale gruppo non si sono notate presenze di feci diarroiche per tutta la durata del trattamento per cui i risultati si riferiscono unicamente ai due gruppi trattati con i lassativi. Each group consisted of 10 animals, one group was also kept as a control and treated with only suspending agent (gum arabic), in this group there were no presences of diarrheal feces for the entire duration of the treatment so the results were refer only to the two groups treated with laxatives.
I risultati sono contenuti nell'allegata tabella 2. The results are contained in the attached table 2.
TABELLA 2 Attività lassativa (Schmidt e coli.) TABLE 2 Laxative activity (Schmidt and coli.)
MX GX MX GX
5 h 5 h
7,5 h 7.5 h
24h 24h
30 h 30 h
5h 5h
7,5 h 7.5 h
24h 24h
30 h 30 h
1 1
+ + + +
+ + + +
+ + + + + +
+ +
+ + + + + +
+ + + + + +
+ + + +
— -
2 2
+ +
+ + + +
+ + + +
— -
+ + + +
+ + + +
+ + + +
— -
3 3
+ + + + + +
+ + + + + +
+ + + + + +
— -
+ +
+ +
+ + + + + +
— -
4 4
+ + + +
+ + + +
+ + + +
— -
+ + + + + +
+ + + + + +
+++++ +++++
— -
5 5
+ + + +
+ + + + + +
+ + + +
— -
+ + + +
+ + + +
+ + + +
— -
6 6
— -
+ +
+ +
— -
+ + + + + + + +
+ + + + + + + +
+ + + + + + + +
— -
7 7
+ + + +
+ + + +
+ + + +
+ +
— -
+ +
+ + + +
— -
8 8
+ + + +
+ + + +
+ +
— -
+ + + + + +
+ + + + + +
+ + + +
+ + + +
9 9
+ + + + + +
+ + + + + +
+ + + +
— -
+ + + + + + + +
+ + + + + + + +
+ + + + + + + +
— -
10 10
+ + + + + +
+ + + + + +
+ + + +
— -
+ + + + + + + +
+ + + + + + + +
+ + + + + + + +
— -
Media % 2,0 Average% 2.0
2,3 2.3
2,0 2.0
0,3 0.3
2,5 2.5
2,6 2.6
2,9 2.9
0,2 0.2
animali animals
diarroici diarrheal
90% 90%
100% 100%
100% 100%
30% 30%
90% 90%
100% 100%
100% 100%
10% 10%
La durata dell'azione lassativa di GX e MX è stata determinata nel ratto per una dose di 37,5 mg/kg/os. The duration of the laxative action of GX and MX was determined in the rat for a dose of 37.5 mg / kg / os.
I risultati dell'esperienza sono contenuti nella tabella 3 qui di seguito riportata. The results of the experience are contained in table 3 below.
TABELLA 3 TABLE 3
Durata dell'azione lassativa di GX e MX Duration of the laxative action of GX and MX
Animali n. Animals n.
Trattamento Treatment
Durata di tempo nella quale l'animale risulta diarroico (n. dee. ± d.s.) Duration of time in which the animal is diarrheal (n.dee. ± d.s.)
10 10
Mucillagine Mucilage
0 0
controllo control
10 10
GX 37,5 mg/kg GX 37.5 mg / kg
27,6 + 1,77 27.6 + 1.77
per os per os
10 10
MX 37,5 mg/kg MX 37.5 mg / kg
27,7 ± 2,54 27.7 ± 2.54
per os per os
Come risulta dalla precedente documentazione, il Mepilax presenta un'azione in tutto e per tutto simile a quella del Sodium Picosulfate, che è uno dei lassativi attualmente più utilizzati, e che presenta un'evidente analogia strutturale con il composto secondo l'invenzione. As can be seen from the previous documentation, Mepilax has an action in all respects similar to that of Sodium Picosulfate, which is one of the most widely used laxatives, and which has a clear structural analogy with the compound according to the invention.
Tuttavia, la tabella 1 pone in evidenza la superiorità del composto secondo l'invenzione, per la più prolungata azione. Questo dato trova riscontro nella sperimentazione condotta sull'uomo. Infatti, a più di 30 pazienti di ambo i sessi, e di età media sui trent'anni, normalmente affetti da stitichezza, sono stati somministrati in tempi diversi entrambi i farmaci. Si è riscontrata una tollerabilità significativamente assai maggiore nei confronti del Mepilax. In particolare, circa il 75 % dei pazienti ha osservato una azione notevol- However, table 1 highlights the superiority of the compound according to the invention, for the most prolonged action. This fact is reflected in the experimentation conducted on man. In fact, more than 30 patients of both sexes, and average age in their thirties, normally suffering from constipation, have been given both drugs at different times. Significantly much greater tolerability was found against Mepilax. In particular, about 75% of patients observed a remarkable action
5 5
10 10
15 15
20 20
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30 30
35 35
40 40
45 45
50 50
55 55
60 60
65 65
646 692 646 692
4 4
mente più prolungata e assai meno violenta del Mepilax, ministrazione (capsule, confetti, supposte), contenenti da 3 more prolonged and much less violent mind than Mepilax, ministration (capsules, sugared almonds, suppositories), containing 3
in confronto con l'altro farmaco. Quasi tutti i pazienti han- a 10 mg di principio attivo, unitamente agli eccipienti usuano altresì osservato una netta diminuzione di dolori e di li; inoltre, una formulazione in gocce (mezzo idroglicerico) effetti collaterali nel caso di assunzione dei Mepilax. tale da consentire l'assunzione di quantità equivalenti di in comparison with the other drug. Almost all patients have a 10 mg of active ingredient, together with the excipients also observed a marked decrease in pain and pain; in addition, a drop formulation (hydroglyceric medium) side effects in the case of taking Mepilax. such as to allow the assumption of equivalent quantities of
Si prevedono per quest'ultimo le abituali forme di som- 5 principio attivo in 5-15 gocce. The usual forms of active ingredient in 5-15 drops are foreseen for the latter.
v v
Claims (4)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT23571/79A IT1121574B (en) | 1979-06-14 | 1979-06-14 | NEW COMPOUND WITH LAXATION ACTIVITY, PROCESS FOR ITS PREPARATION AND PHARMACEUTICAL COMPOSITIONS THAT CONTAIN IT |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH646692A5 true CH646692A5 (en) | 1984-12-14 |
Family
ID=11208226
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH456780A CH646692A5 (en) | 1979-06-14 | 1980-06-13 | PYRIDYLMETHANE DERIVATIVE WITH LAXATIVE ACTIVITY, PROCESS FOR ITS PREPARATION AND PHARMACEUTICAL COMPOSITIONS THAT CONTAIN IT. |
Country Status (11)
| Country | Link |
|---|---|
| JP (1) | JPS568366A (en) |
| AR (1) | AR223223A1 (en) |
| BE (1) | BE883804A (en) |
| CH (1) | CH646692A5 (en) |
| DE (1) | DE3021785A1 (en) |
| ES (1) | ES8104799A1 (en) |
| FR (1) | FR2459232A1 (en) |
| GB (1) | GB2051801B (en) |
| IT (1) | IT1121574B (en) |
| MX (1) | MX5881E (en) |
| NL (1) | NL8003465A (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6222690Y2 (en) * | 1980-10-21 | 1987-06-09 | ||
| JPS5872747A (en) * | 1981-10-28 | 1983-04-30 | Nissan Motor Co Ltd | Rear mounting device for power unit |
| IT1167197B (en) * | 1983-07-25 | 1987-05-13 | Bellon Roger Schoum Rbs Pharma | USE OF PHENPYRAMIN AS A PLATELET ANTI-AGGREGATING, VASODILATOR, ANTI-THROMBOTIC AND ANTI-ANGLE DRUG |
| JPH01283222A (en) * | 1988-05-10 | 1989-11-14 | Tokai Kapuseru Kk | Soft capsule agent of sodium picosulfate |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB730243A (en) * | ||||
| FR75159E (en) * | 1961-09-08 | |||
| US2764590A (en) * | 1952-03-17 | 1956-09-25 | Thomae Gmbh Dr K | Certain 4, 4'-disubstituted-diphenylpyridyl methanes and process |
-
1979
- 1979-06-14 IT IT23571/79A patent/IT1121574B/en active
-
1980
- 1980-06-10 DE DE19803021785 patent/DE3021785A1/en active Granted
- 1980-06-10 GB GB8018930A patent/GB2051801B/en not_active Expired
- 1980-06-12 MX MX808872U patent/MX5881E/en unknown
- 1980-06-13 JP JP8082880A patent/JPS568366A/en active Granted
- 1980-06-13 ES ES492397A patent/ES8104799A1/en not_active Expired
- 1980-06-13 NL NL8003465A patent/NL8003465A/en not_active Application Discontinuation
- 1980-06-13 CH CH456780A patent/CH646692A5/en not_active IP Right Cessation
- 1980-06-13 FR FR8013234A patent/FR2459232A1/en active Granted
- 1980-06-13 AR AR281393A patent/AR223223A1/en active
- 1980-06-13 BE BE2/58605A patent/BE883804A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| AR223223A1 (en) | 1981-07-31 |
| GB2051801A (en) | 1981-01-21 |
| DE3021785A1 (en) | 1980-12-18 |
| NL8003465A (en) | 1980-12-16 |
| DE3021785C2 (en) | 1988-04-28 |
| IT7923571A0 (en) | 1979-06-14 |
| JPS5745431B2 (en) | 1982-09-28 |
| JPS568366A (en) | 1981-01-28 |
| GB2051801B (en) | 1983-03-09 |
| ES492397A0 (en) | 1981-05-16 |
| MX5881E (en) | 1984-08-16 |
| FR2459232B1 (en) | 1984-05-18 |
| IT1121574B (en) | 1986-04-02 |
| FR2459232A1 (en) | 1981-01-09 |
| BE883804A (en) | 1980-10-01 |
| ES8104799A1 (en) | 1981-05-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |