LU81582A1 - PYRAZOLIDINE-DIONE DERIVATIVES AND THEIR THERAPEUTIC APPLICATION - Google Patents
PYRAZOLIDINE-DIONE DERIVATIVES AND THEIR THERAPEUTIC APPLICATION Download PDFInfo
- Publication number
- LU81582A1 LU81582A1 LU81582A LU81582A LU81582A1 LU 81582 A1 LU81582 A1 LU 81582A1 LU 81582 A LU81582 A LU 81582A LU 81582 A LU81582 A LU 81582A LU 81582 A1 LU81582 A1 LU 81582A1
- Authority
- LU
- Luxembourg
- Prior art keywords
- pyrazolidine
- dione
- therapeutic application
- dione derivatives
- compounds
- Prior art date
Links
- CYMJPJKHCSDSRG-UHFFFAOYSA-N pyrazolidine-3,4-dione Chemical class O=C1CNNC1=O CYMJPJKHCSDSRG-UHFFFAOYSA-N 0.000 title claims description 6
- 230000001225 therapeutic effect Effects 0.000 title description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 239000013638 trimer Substances 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 239000004305 biphenyl Substances 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- -1 piperazino, piperidino Chemical group 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 230000004931 aggregating effect Effects 0.000 description 1
- 229940127218 antiplatelet drug Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/28—Two oxygen or sulfur atoms
- C07D231/30—Two oxygen or sulfur atoms attached in positions 3 and 5
- C07D231/32—Oxygen atoms
- C07D231/36—Oxygen atoms with hydrocarbon radicals, substituted by hetero atoms, attached in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
1·. ί· CZO1 ·. ί · CZO
La présente invention concerne des dérivés de pyrazolidine-dione, leur préparation et leur application en thérapeutique.The present invention relates to pyrazolidine-dione derivatives, their preparation and their therapeutic use.
H Les composés de l'invention répondent à la formule S 0 ; -A -O ” I - SO - (CH2)2--Lo I · CH2 - “s.H The compounds of the invention correspond to the formula S 0; -A -O ”I - SO - (CH2) 2 - Lo I · CH2 -“ s.
î 2 dans laquelle et R2 représentent chacun, indépendamment l'un de l'autre, un 0 atome d'hydrogène, un radical alkyle de 1 à 6 atomes de carbone ou k a ^ NR1R2 f°ment ensemble un hétérocycle pouvant ou non contenir un autre hétéroatome qui peut lui même porter un substituant.î 2 in which and R2 each represent, independently of one another, a hydrogen atom, an alkyl radical of 1 to 6 carbon atoms or ka ^ NR1R2 together form a heterocycle which may or may not contain a another heteroatom which can itself carry a substituent.
Les radicaux hétérocycliques peuvent être les radicaux morpholino, * pipérazino, pipéridino et plus particulièrement le radical méthyl-4 .5 oipérazino-l.The heterocyclic radicals can be the morpholino, * piperazino, piperidino and more particularly the methyl-4 .5 oiperazino-1 radical.
! — *-. - j * .! - * -. - j *.
I ; 'I; ''
Selon l'invention, on prépare les composés par réaction entre la pyrazolidine-dione (II) c? l. · % 6-·» i ' 'j ^ (II)According to the invention, the compounds are prepared by reaction between pyrazolidine-dione (II) c? l. ·% 6- · ”i '' j ^ (II)
>0 ^ \- S - (ch2)2 —_LlO> 0 ^ \ - S - (ch2) 2 —_LlO
I, ! I . .I,! I. .
Il âavec du formaldéhyde ou son trimère et une amine HN (III).It with formaldehyde or its trimer and an HN (III) amine.
BB
k ;Vhk; Vh
. - CIZI. - CIZI
» L'exemple suivant illustre l'invention.The following example illustrates the invention.
Les analyses et spectres IR et RMN confirment la structure du composé.The IR and NMR analyzes and spectra confirm the structure of the compound.
Exemple Diphényl-1,2 (phënyl-sulflnyl-2 éthyl)-4 £(mëthyl-4 5 pipérazino)-méthylJ-4 pyrazolidine-dione-3,5.Example 1,2-Diphenyl (2-phenyl-2-sulfylethyl) -4 £ (4-methylpiperazino) -methylJ-4 pyrazolidine-dione-3,5.
bn agite une solution de 4,044 g (0,01 mole) de diphényl-1,2 (phény!.bn agitates a solution of 4.044 g (0.01 mole) of 1,2-diphenyl (pheny !.
jsulfînyl-2 éthyl)-4 pyrazolidine-dione-3,5, 10 cm d*isopropanol, i 3 11,048cm de formaldéhyde et 1,23 cm (0,0111 mole) de N-méthyl-pipé-•razine. La température s'élève à + 29°C.2-sulfylethyl (ethyl) -4 pyrazolidine-dione-3.5, 10 cm isopropanol, i 3 11.048 cm formaldehyde and 1.23 cm (0.0111 mole) N-methyl-piperazine. The temperature rises to + 29 ° C.
ΙΟΙ bn chauffe à la température de reflux pendant 2 heures 30.ΙΟΙ bn heats at reflux temperature for 2 hours 30 minutes.
Dn évapore le solvant et on reprend par du chloroforme que l'on sèche sur MgSO^. On évapore le chloroforme et on dissout le résidu d'évaporation dans de l'éther au reflux.The solvent is evaporated off and the residue is taken up in chloroform which is dried over MgSO 4. The chloroform is evaporated and the evaporation residue is dissolved in ether at reflux.
On sépare l'insoluble et on évapore l'éther.The insoluble material is separated and the ether is evaporated.
15 jOn obtient un produit balnc.15 jWe obtain a balnc product.
» F = 139ÖC."F = 139ÖC.
Les essais pharmacologiques effectués sur les composés de l'invention montrent qu'ils sont actifs comme antiagrégants plaquettaires.Pharmacological tests carried out on the compounds of the invention show that they are active as antiplatelet agents.
L'inhibition de l'agrégation plaquettaire a été mesurée sur des 20 plaquettes de lapin, in vitro , selon le test de Born et Cross, J. Physiol. 1963, 168-178 ; l'ADP et le collagène étant utilisés comme agents agrégants.The inhibition of platelet aggregation was measured on rabbit platelets, in vitro, according to the test of Born and Cross, J. Physiol. 1963, 168-178; ADP and collagen being used as aggregating agents.
ss
En présence d'ADP la CA 50 exprimée en pg/ml est d'environ 400 pour le composé de l'invention étudié à titre d'exemple. En présence de 25 collagène la CA 50 est d'environ 135 jig/ml.In the presence of ADP the CA 50 expressed in pg / ml is approximately 400 for the compound of the invention studied by way of example. In the presence of collagen the CA 50 is about 135 jig / ml.
Les composés de l'invention peuvent être utilisés pour le traitement de l'agrégation plaquettaire.The compounds of the invention can be used for the treatment of platelet aggregation.
s*·.s * ·.
VV
’ ______ ______ — - 1 I ' ε3=] I r ;[L'invention comprend toutes compositions pharmaceutiques renfermant ! iau moins l'un des composés (I) comme principe actif, en association 'avec tous excipients appropriés à leur administration, principale-:§ ment par voie orale, mais aussi Dar voie endorectale ou parentérale lié r’______ ______ - - 1 I 'ε3 =] I r; [The invention includes all pharmaceutical compositions containing! ia at least one of the compounds (I) as active principle, in association with all the excipients suitable for their administration, mainly-: § ment orally, but also Dar endorectal or parenteral route linked r
If < ^ \ Ψ ..h ^If <^ \ Ψ ..h ^
AAT
k T>j; ; i... i * 1 ! t ¥k T> j; ; i ... i * 1! t ¥
I 1 jJI 1 dd
I 'i Λ“" -, A $ 'T*I 'i Λ “" -, A $' T *
PP
§1 1 > IÎ i§1 1> IÎ i
HH
' * kl 1 - V _——'* kl 1 - V _——
Claims (3)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7823438A FR2433020A1 (en) | 1978-08-09 | 1978-08-09 | PYRAZOLIDINE-DIONE DERIVATIVES AND THEIR THERAPEUTIC APPLICATION |
| FR7823438 | 1978-08-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| LU81582A1 true LU81582A1 (en) | 1981-03-24 |
Family
ID=9211717
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| LU81582A LU81582A1 (en) | 1978-08-09 | 1979-08-08 | PYRAZOLIDINE-DIONE DERIVATIVES AND THEIR THERAPEUTIC APPLICATION |
Country Status (11)
| Country | Link |
|---|---|
| JP (1) | JPS5524200A (en) |
| AT (1) | AT369735B (en) |
| BE (1) | BE878158A (en) |
| DE (1) | DE2932054A1 (en) |
| ES (1) | ES483236A1 (en) |
| FR (1) | FR2433020A1 (en) |
| GB (1) | GB2028324A (en) |
| IT (1) | IT1122740B (en) |
| LU (1) | LU81582A1 (en) |
| NL (1) | NL7906029A (en) |
| PT (1) | PT70042A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1191034B (en) * | 1982-10-15 | 1988-02-24 | Edmondo Pharma Srl | COMPOUND WITH VASODILATOR, ANTI-AGGREGATING AND HYPO-COLESTEROLEMIZING ACTIVITY, PROCEDURE FOR ITS PREPARATION AND RELATIVE PHARMACEUTICAL COMPOSITION |
-
1978
- 1978-08-09 FR FR7823438A patent/FR2433020A1/en active Granted
-
1979
- 1979-08-07 DE DE19792932054 patent/DE2932054A1/en not_active Withdrawn
- 1979-08-07 AT AT0539279A patent/AT369735B/en not_active IP Right Cessation
- 1979-08-07 GB GB7927472A patent/GB2028324A/en not_active Withdrawn
- 1979-08-07 NL NL7906029A patent/NL7906029A/en not_active Application Discontinuation
- 1979-08-08 IT IT24997/79A patent/IT1122740B/en active
- 1979-08-08 PT PT70042A patent/PT70042A/en unknown
- 1979-08-08 LU LU81582A patent/LU81582A1/en unknown
- 1979-08-08 JP JP10178979A patent/JPS5524200A/en active Pending
- 1979-08-08 ES ES483236A patent/ES483236A1/en not_active Expired
- 1979-08-09 BE BE0/196660A patent/BE878158A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IT1122740B (en) | 1986-04-23 |
| FR2433020A1 (en) | 1980-03-07 |
| AT369735B (en) | 1983-01-25 |
| JPS5524200A (en) | 1980-02-21 |
| FR2433020B1 (en) | 1980-12-05 |
| GB2028324A (en) | 1980-03-05 |
| ATA539279A (en) | 1982-06-15 |
| DE2932054A1 (en) | 1980-02-21 |
| ES483236A1 (en) | 1980-05-16 |
| IT7924997A0 (en) | 1979-08-08 |
| NL7906029A (en) | 1980-02-12 |
| PT70042A (en) | 1979-09-01 |
| BE878158A (en) | 1980-02-11 |
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