DE2428409C3 - S3'-Bis-(3-hydroxy-4-hydroxymethyl-2-methyl-5-pyridylmethyl)-carbonodithioat, dessen pharmakologisch verträgliche Salze und Arzneimittel - Google Patents
S3'-Bis-(3-hydroxy-4-hydroxymethyl-2-methyl-5-pyridylmethyl)-carbonodithioat, dessen pharmakologisch verträgliche Salze und ArzneimittelInfo
- Publication number
- DE2428409C3 DE2428409C3 DE2428409A DE2428409A DE2428409C3 DE 2428409 C3 DE2428409 C3 DE 2428409C3 DE 2428409 A DE2428409 A DE 2428409A DE 2428409 A DE2428409 A DE 2428409A DE 2428409 C3 DE2428409 C3 DE 2428409C3
- Authority
- DE
- Germany
- Prior art keywords
- bis
- methyl
- hydroxymethyl
- hydroxy
- pyridylmethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- 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
- C07D213/60—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 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
- C07D213/66—One oxygen atom attached in position 3 or 5 having in position 3 an oxygen atom and in each of the positions 4 and 5 a carbon atom bound to an oxygen, sulphur, or nitrogen atom, e.g. pyridoxal
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
-
- 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
- C07D213/26—Radicals substituted by halogen atoms or nitro radicals
-
- 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
- C07D213/32—Sulfur atoms
-
- 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
- C07D213/60—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 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
-
- 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
- C07D213/60—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 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/70—Sulfur atoms
-
- 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
- C07D213/60—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 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
- 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
- C07D213/89—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 with hetero atoms directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D327/00—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms
- C07D327/02—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms one oxygen atom and one sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D497/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having oxygen and sulfur atoms as the only ring hetero atoms
- C07D497/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having oxygen and sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D497/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Rheumatology (AREA)
- Pharmacology & Pharmacy (AREA)
- Pain & Pain Management (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pyridine Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
sowie deren pharmakologiseh verträgliche Salze. 2. Arzneimittel, bestehend aus einer Verbindung
gemäß Anspruch I und üblichen Träger-. Hilfs- und Verdünnungsmitteln.
R1OCHv
CH3
CH2OR2
Ii A ORl
-S-C-S-CH2-I[V7
in der Kx und R2 gleich oder verschieden sind und jeweils
ein WasserstofTatom oder eine säureempfindliche Schutzgruppe (wie eine Tetrahydropyranylgruppe)
bedeuten oder R, und R2 zusammen einen Rest der nachstehenden allgemeinen Formel bilden
Ungeachtet der intensiven Forschung der letzten zwei Jahrzehnte auf dem Gebiet der entzündungshemmenden
Mittel besteht weiterhin Bedarf an einem wirksamen und gut verträglichen Arzneimittel gegen
rhcumatoide Arthritis. Die herkömmlichen, keine Steroide darstellenden, gleichzeitig entzündungshemmend,
analgctisch imduniipyrclisch wirkenden Mittel,
wie Acetylsalicylsäurc, sowie viele neue, im Stadium klinischer Untersuchung stehende Arzneisioffe ermöglichen
lediglich eine symptomatische Milderung des akuten Syndroms, sind jedoch nicht in der Lage,
den Krankheilsverlauf zu ändern. Demgemäß haben die antirheumatischen Wirkungsweisen zweier aller
Heilmittel, nämlich von Gold und D-Pcnicillamin. trotz ihrer potentiellen Nebenwirkungen in den letzten
Jahren neues Interesse gefunden. Die klinische Wirksanikeil
beider Heilmittel wurde an Hand sorgfältiger, an mehreren Stellen durchgeführter klinischer Untersuchungen
neuerlich bestätigt. Mehrere Rheumatologen haben die Auffassung vertreten, daß eine D-penicillaminähnliehc
Verbindung mil überdurchschnittlichen Eigenschaften die Medizin auf diesem bedeutsamen
Gebiet außerordentlich bereichern würde.
Die Erfindung belriffi die Verbindung der Formel
CH7OH
f Y-CH1 S-C S
CH,
C Ή, Ο Η
OH
OH
sowie deren pharmakologiseh vertragliche Salze.
Beispiele für pharmakologiseh verträgliehe Additionssal/e
sind jene, die aus den üblicherweise in der
l'harma/ie verwendeten Mineralsäuren und organischen
Säuren, w ie SaI/-. Bromwassersiofl-. Schwelel-,
Salpeter-. Malein-. l;nniar-. Wem- oder Bernsieinsiiure.
hergestellt werden.
Das erlindungsgemäße S.S - Bis - {} - hvdroxv-4
- hvdrownicllnl - .1 - met In I - 5 - pvridvlmetlnl)-carin
der R, und R4 gleich oder verschieden sind und je-
2) weils ein Wassersloffatom, einen C, -,-Alkylresl oder
eine Phenylgruppc darstellen, mit verdünnter Mineralsäure bei 20 bis 50" C während 1 bis 5 Stunden hergestellt
werden.
Die erfindungsgemäße Verbindung und deren Salze zeigen ein hohes Ausmaß an Wirksamkeit gegenüber
rheumatoider Arthritis.
Wie der nachfolgende Verglcichsvcrsuch zeigt, entfalten zwei pharmakologiseh verträgliche Salze der
crfindungsgemäßen Verbindung dieselbe Wirksam-
!■-. keil wie 5-Mcrcaptopyridoxin bei einem Drittel der
Dosis. Die Toxizität der crlindungsgemäßcn Verbindung und ihrer pharmakologiseh verträglichen Salze
ist ferner wesentlich geringer als jene von 5-Mcrcaplopyridoxin.
κι Die Erfindung betrifft ferner Arzneimittel, welche aus der erfindungsgemäßen Verbindung oder einem
pharmakologiseh verträglichen Salz davon und üblichen Träger-, Hilfs- und Verdünnungsmitteln bestehen.
4") Man kann diese Arzneimittel für die obigen Zwecke
oral, lokal, parenteral, mit Hilfe von Inhalalionssprays oder rektal in Form von Einheitsdosen verabfolgen.
»Parenteral« schließt hier subkutane Injektionen, die intravenöse, intramuskuläre und intrasler-
")ii nale Injektion, die inlraartikuläre Verabfolgung sowie
die Infusionsmethode ein. Außer für die Humanmedizin eignen sich die erlindungsgemüßcn Arzneimittel
auch Tür die Behandlung von warmblütigen Tieren, wie Mäusen, Rallen, Pferden, Hunden, Katzen, Meer-
T) schweinchen oder Kaninchen.
Zur Behandlung der vorgenannten Erkrankungen können Dosen in der Größenordnung von I bis
140 mg/kg Körpergewicht/Tag angewendet werden. Im allgemeinen licgl die wirksame Dosis im Bereich
«ι von 5 bis 50 mg/kg Körpergewicht/Tag.
Hs sei jedoch festgestellt, daß die spezielle Dosis für jeden bestimmten Patienten von den verschiedensten
Faktoren abhängt, beispielsweise von der Wirksamkeil der eingesetzten speziellen Verbindung.
ι-■ vom Aller. Körpergewicht, allgemeinen Gesundheitszustand.
Gcsclilechl. von der Kost, vom Verahfolgungszeitpunkl
und -weg. von der Ausscheidungslieschw
indiukcit. Arzneistolfkombinaiion und Schwere
der jeweiligen Erkrankung, welcher die Therapie gilt.
Das nachstehende Beispiel erläutert die Erfindung.
S,S'-Bis-(3-hydroxy-4-hydroxymethyl-
2-methyl-5-pyridyimethyl)-carbonodithioat-
dihydrochlorid-monohydrat
Stufe A
Herstellung von S,S'-Bis-(2,2,8-lrimethyl-
4H-l,3-dioxino[4,5-c]pyridin-5-yl-methyl)-
carbonodithioat
Eine eisgekühlte Lösung von 4,5 g 5-Mercaptomethyl-2,2,8-trimelhyl-4H-l,3-dioxino[4,5-c]pyridin
in 50 ml wasserfreiem Pyridin wird tropfenweise mit 10 ml einer 12,5prozentigen Phosgenlösung in Benzol
versetzt. Man läßt das Reaklionsgemisch sich auf Raumtemperatur erwärmen und rührt 3 Stunden,
wonach man den Ansatz im Vakuum eindampft. Der Rückstand wird einer Extraktion mit Benzol und gesättigter
Natriumbicarbonallösung unterworfen. Die Benzolschicht wird abgetrennt, mit Wasser gewaschen,
über Natriumsulfat getrocknet und im Vakuum eingedampft. Man Chromatographien den erhaltenen
Rückstand an 250 g Kicsclgcl. Die Elution mit Äther
ergibt 3,59 g S,S'-Bis-(2,2,8-lrimcthyl-4H- 1,3-dioxino[4,5 - c]pyridin - 5 - yl - methyl)- earbonodithioal
vom Fp. 88 bis WC.
Stufe B
Herstellung von S,S'-Bis-(3-hydroxy-4-hydroxymcthyl-2-mcthyl-5-pyridylmelhyl)-carboiuidithioal-dihydrochlorid-monohydrat
Eine Lösung von 0,2 g S,S'-Bis-|2,2,8-lrimelhyl-4H- l^-dioxiiio^.S-cJpyridin-S-yl-mclhyll-carbonodilhioat
in 0,9 ml eiskalter konzentrierter Salzsäure wird 5 Minuten kalt gerührt und anschließend mil
2,5 ml Methanol verdünnt. Beim Abkühlen in Eis/ Aceton bildet sich ein kristalliner Niederschlug, den
man abliltricrt. Man erhält 0,12 g S,S'-Bis-(3-hydroxy-4-hydroxymcthyl-2-mclhyl-5-pyridylmethyl)-carbonodithioat-dihydrochlorid-monohydrat
vom Fp. 125 bis 130 C.
Der nachstehende Vcrglcichsvcrsuch veranschaulich I die überlegene Wirksamkeil der crfindimgsgcmüüen
Verbindungen gegenüber einem bekannten Wirkstoff, nämlich S-Mcrcaptopyridoxin.
Vergleichsversuch
Gruppen von 4 Meerschweinchen erhielten oral zur Zeit 0 30 mg/kg oder 90 mg/kg der 'lötverbindung.
Jedes Tier erhielt eine zweite Dosis der Tesl-
| Dosis | Durch | % Inhi |
| messer | bierung | |
| Erythem | ||
| (mg/kg) | (mm) | |
| ._„ | 11,1 | - |
| 90 | 7,6 | 32 |
| 30 | 7,2 | 36 |
verbindung in der gleichen Menge 17 Stunden später.
Eine Stunde nach Gabe der zweiten Dosis der Testverbindung erhielt jedes Tier intradermal Lymphokine
(lösliche Proteinmittler, freigesetzt durch sensibilisierte Lymphocyten bei Kontakt mit Antigen).
22 Stunden später wurde an der Injektionsstelle der Umfang des Erythems gemessen.
|0 Behandlung
Salz
5-Mercaptopyridoxin
S,S'-Bis-(3-hydroxy-
4-hydroxymethyl-
2-methyl-5-pyridylmcthyU-carbono-
dithioat-dihydrochlorid
S,S'-Bis-(3-hydroxy- 30 7,5 34*)
4-hydroxymethyl-,r
2-methyl-5-pyridyl-
melhyO-carbono-
dithioat-sulfat-
halbhydral
·) Statistische Signifikanz P < 0,05.
Sowohl das Sulfat als auch das Dihydrochlorid
von S,S'-Bis-(3-hydroxy-4-hydroxymcthyl-2-melhyl-5-pyridylmethyl)-carbonodithioat
zeigen also etwa die
η gleiche Wirksamkeit wie 5-Mercaptopyridoxin bei einem Drittel der Dosis des 5-Mercaptopyridoxins.
Die geringere Toxizität der erfindungsgemäßen
Verbindung und ihrer Salze geht aus der nachstehenden Gegenüberstellung hervor:
LD51, (weibliche Mäuse des Stammes CF1S orale
Gabe in Wasser)
Dihydrochlorid der erfindungs-
4. gemäßen Verbindung 6910 mg/kg
5-Mercaplopyridoxin-
hydrochlorid 1250 mg/kg
LD5n (weibliche Mäuse des Stammes CF1S orale
Gabe in I %iger wäßriger Methylcellulose)
Hrfindungsgemäße
Verbindung >685O mg kg
Sulfat-Halbhydrat der
erlindungsgemäßen Verbindung 8870 mg/kg
Claims (1)
1. S,S'-Bis-(3-hydroxy-4-hydroxymethyI-2-methyl-5-pyridylmethyl)-ca;bonodithioat
der Formel
CH,OH
CH,OH
HO—/ V-CH1-S-C-S-CH,
bonodithioat kann durch Hydrolyse einer Verbindung der nachstehenden allgemeinen Formel
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36877473A | 1973-06-15 | 1973-06-15 | |
| US05/470,231 US3971797A (en) | 1973-06-15 | 1974-05-16 | S,S'-bis(pyridylmethyl)-carbonodithioates |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE2428409A1 DE2428409A1 (de) | 1975-01-09 |
| DE2428409B2 DE2428409B2 (de) | 1978-11-30 |
| DE2428409C3 true DE2428409C3 (de) | 1979-08-09 |
Family
ID=27004328
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19742428294 Ceased DE2428294A1 (de) | 1973-06-15 | 1974-06-12 | Mercaptomethylpyridine und derivate derselben |
| DE2428409A Expired DE2428409C3 (de) | 1973-06-15 | 1974-06-12 | S3'-Bis-(3-hydroxy-4-hydroxymethyl-2-methyl-5-pyridylmethyl)-carbonodithioat, dessen pharmakologisch verträgliche Salze und Arzneimittel |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19742428294 Ceased DE2428294A1 (de) | 1973-06-15 | 1974-06-12 | Mercaptomethylpyridine und derivate derselben |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US3971797A (de) |
| JP (3) | JPS5032180A (de) |
| AR (1) | AR203749A1 (de) |
| BG (1) | BG24408A3 (de) |
| CA (1) | CA1037956A (de) |
| CH (4) | CH613951A5 (de) |
| DD (1) | DD113001A5 (de) |
| DE (2) | DE2428294A1 (de) |
| DK (1) | DK148595C (de) |
| ES (1) | ES427277A1 (de) |
| FI (1) | FI58775C (de) |
| FR (2) | FR2233056B1 (de) |
| GB (2) | GB1466386A (de) |
| IE (1) | IE39467B1 (de) |
| IL (1) | IL44998A (de) |
| LU (1) | LU70342A1 (de) |
| NL (2) | NL7407618A (de) |
| NO (1) | NO144149C (de) |
| PH (1) | PH10366A (de) |
| RO (2) | RO71434A (de) |
| SE (1) | SE411346B (de) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4061759A (en) * | 1975-05-19 | 1977-12-06 | Merck & Co., Inc. | Ethenyl and ethynyl mercaptoalkyl pyridines |
| CH655110A5 (de) * | 1982-09-03 | 1986-03-27 | Otsuka Pharma Co Ltd | Carbostyrilderivate, verfahren zu deren herstellung und arzneimittel, welche diese enthalten. |
| EP0640072B1 (de) * | 1992-05-15 | 2000-08-23 | Btg International Limited | Pyridinderivate als Hydroxylase- und Lyase-Inhibitoren |
| GB2266887B (en) * | 1992-05-15 | 1996-04-17 | British Tech Group | Substituted pyridines,their preparation and pharmaceutical use |
| GB201718148D0 (en) * | 2017-11-02 | 2017-12-20 | Ipotts Ltd | Hair cutting comb |
| GB2603007B (en) * | 2021-01-26 | 2023-01-11 | Pickuls Gizmo Ltd | A hair cutting guide |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3515726A (en) * | 1968-10-16 | 1970-06-02 | Olin Mathieson | 2,2'-bis(pyridyl-n-oxide) dithiolcarbonates and trithiocarbonates |
-
1974
- 1974-05-16 US US05/470,231 patent/US3971797A/en not_active Expired - Lifetime
- 1974-06-03 FI FI1685/74A patent/FI58775C/fi active
- 1974-06-04 SE SE7407296A patent/SE411346B/xx not_active IP Right Cessation
- 1974-06-06 NL NL7407618A patent/NL7407618A/xx not_active Application Discontinuation
- 1974-06-06 NL NLAANVRAGE7407616,A patent/NL185841C/xx not_active IP Right Cessation
- 1974-06-06 NO NO742042A patent/NO144149C/no unknown
- 1974-06-06 DK DK303274A patent/DK148595C/da not_active IP Right Cessation
- 1974-06-10 IL IL44998A patent/IL44998A/en unknown
- 1974-06-10 PH PH15930A patent/PH10366A/en unknown
- 1974-06-10 CA CA202,346A patent/CA1037956A/en not_active Expired
- 1974-06-11 IE IE1219/74A patent/IE39467B1/xx unknown
- 1974-06-12 GB GB2617674A patent/GB1466386A/en not_active Expired
- 1974-06-12 GB GB2617874A patent/GB1466295A/en not_active Expired
- 1974-06-12 DE DE19742428294 patent/DE2428294A1/de not_active Ceased
- 1974-06-12 DE DE2428409A patent/DE2428409C3/de not_active Expired
- 1974-06-13 FR FR7420548A patent/FR2233056B1/fr not_active Expired
- 1974-06-13 CH CH812274A patent/CH613951A5/xx not_active IP Right Cessation
- 1974-06-13 FR FR7420549A patent/FR2233057B1/fr not_active Expired
- 1974-06-14 ES ES427277A patent/ES427277A1/es not_active Expired
- 1974-06-14 AR AR254190A patent/AR203749A1/es active
- 1974-06-14 CH CH821974A patent/CH610305A5/xx not_active IP Right Cessation
- 1974-06-14 RO RO7479181A patent/RO71434A/ro unknown
- 1974-06-14 DD DD179177A patent/DD113001A5/xx unknown
- 1974-06-14 RO RO7490744A patent/RO70852A/ro unknown
- 1974-06-14 BG BG7400026975A patent/BG24408A3/xx unknown
- 1974-06-15 JP JP49067657A patent/JPS5032180A/ja active Pending
- 1974-06-15 JP JP49067658A patent/JPS5032181A/ja active Pending
- 1974-06-17 LU LU70342A patent/LU70342A1/xx unknown
-
1978
- 1978-01-13 JP JP209778A patent/JPS5387363A/ja active Granted
- 1978-03-20 CH CH303278A patent/CH634302A5/de not_active IP Right Cessation
- 1978-09-18 CH CH972578A patent/CH618428A5/de not_active IP Right Cessation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE60011391T2 (de) | Verfahren und zusammensetzungen zur erhöhung der anzahl weisser blutzellen | |
| DE69016821T2 (de) | Behandlungsmittel gegen Osteoarthritis. | |
| EP0529500B1 (de) | Arzneimittel zur Behandlung von Abstossungsreaktionen bei Organverpflanzungen | |
| DE69029732T2 (de) | Bivalente metallsalze von indomethacin | |
| DE1908991C3 (de) | ||
| DE2428409C3 (de) | S3'-Bis-(3-hydroxy-4-hydroxymethyl-2-methyl-5-pyridylmethyl)-carbonodithioat, dessen pharmakologisch verträgliche Salze und Arzneimittel | |
| DE68915269T2 (de) | Polyvalentes entzündungshemmendes mittel. | |
| DE2166355C2 (de) | Verwendung von d,1-Sobrerol bei der Balsamtherapie der Atemwege | |
| DE1695672C3 (de) | 2-MeUIyM-[^- methoxy-carbonyl)-phenylamino] -7-chlorchinolin und dessen Salze, Verfahren zu deren Herstellung und diese enthaltende Arzneimittel | |
| DE3111593C2 (de) | 3-Desoxy-3-[3-(2-chloräthyl)-3-nitrosoureido]-D-allopyranose, Verfahren zu ihrer Herstellung und diese Verbindung enthaltende Antitumormittel | |
| DE2625053C3 (de) | Arzneimittel zur Kontrolle von Leberkrankheiten | |
| AT407833B (de) | Mittel zur behandlung von strahlenschäden | |
| DE3116029A1 (de) | 3-deazaadenosin als entzuendungshemmendes mittel | |
| DE2953223C2 (de) | ||
| DE1936723C2 (de) | Salze von Chinarindenalkoloiden und Verfahren zu ihrer Herstellung | |
| DE1900772A1 (de) | Dimethylbiguanidderivat | |
| DE2535799B2 (de) | N'- [1 -(p-Chlorbenzoyl)-5-methoxy-2-methyl-3indolyl-acetoxy- alkyl] -N-(N-benzoyl- N',N'-di-npropyl-DL-isoglutaminyloxy- alkyl)-piperazine und diese enthaltene Entzündungen und Gelenksaffektionen hemmende Präparate | |
| DE2145359A1 (de) | Neue Phthalazindenvate | |
| DE2314387C3 (de) | Arzneimittel zur Behandlung bösartiger Neubildungen | |
| DE2630015B2 (de) | 4,5,6,7-Tetrahydro-3-(4-methoxyphenyl)-indazol und diese Verbindung enthaltende Arzneimittel | |
| DE1795782C3 (de) | N-Trityl-imidazole | |
| AT345835B (de) | Verfahren zur herstellung von neuem bis- (2-methyl-3-hydroxy-5-vinylpyridyl-4-methyl)- disulfid-sulfat-monohydrat | |
| DE2416302B2 (de) | Dimeres sowie trimeres silybin und deren n-methylglucaminsalz und verfahren zu deren herstellung sowie diese verbindungen enthaltende arzneimittel | |
| DE19544414A1 (de) | Antimikrobiell wirkende Bismut(V)-Verbindungen mit Tropolonverbindungen und diese enthaltende Arzneimittel | |
| DE3509244A1 (de) | Salze von erythromycin mit essigsaeurederivaten, verfahren zu deren herstellung und diese enthaltende pharmakochemische mischungen |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C3 | Grant after two publication steps (3rd publication) |