DE1966821C3 - Ni.i ^ »> i-N2 - (23.4-trihydroxy-benzylidene) hydrazide and its acid addition salts - Google Patents

Ni.i ^ »> i-N2 - (23.4-trihydroxy-benzylidene) hydrazide and its acid addition salts

Info

Publication number
DE1966821C3
DE1966821C3 DE1966821A DE1966821A DE1966821C3 DE 1966821 C3 DE1966821 C3 DE 1966821C3 DE 1966821 A DE1966821 A DE 1966821A DE 1966821 A DE1966821 A DE 1966821A DE 1966821 C3 DE1966821 C3 DE 1966821C3
Authority
DE
Germany
Prior art keywords
hydrazide
trihydroxy
acid addition
addition salts
benzylidene
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
Application number
DE1966821A
Other languages
German (de)
Other versions
DE1966821B2 (en
DE1966821A1 (en
Inventor
Giuseppe Dr. Basel Bartholini
Balthasar Dr. Binningen Hegedues
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
F Hoffmann La Roche AG
Original Assignee
F Hoffmann La Roche AG
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by F Hoffmann La Roche AG filed Critical F Hoffmann La Roche AG
Publication of DE1966821A1 publication Critical patent/DE1966821A1/en
Publication of DE1966821B2 publication Critical patent/DE1966821B2/en
Application granted granted Critical
Publication of DE1966821C3 publication Critical patent/DE1966821C3/en
Expired legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/72—Hydrazones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C243/00—Compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
    • C07C243/24—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids
    • C07C243/26—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C243/34—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of a carbon skeleton further substituted by nitrogen atoms

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Description

bei Ratten gemessen, wobei sich folgende Werte ergeben:measured in rats, resulting in the following values:

1010

Die Erfindung betrifft ein neues, von L-Serin abgeleitetes Hydrazid der Formel:The invention relates to a new hydrazide derived from L-serine of the formula:

CH=N-NH-CO-CH-CH2Oh (I)CH = N-NH-CO-CH-CH 2 Oh (I)

OHOH

NH2 NH 2

ISIS

2020th

sowie Säureadditionssalze hiervon.and acid addition salts thereof.

Die erfindungsgemäßen Verbindungen sind Zwischenverbindungen zur Herstellung von Ni-L-Seryl-N2-(2,3,4-trihydroxy-benzyl)-hydrazid sowie dessen Säureadditionssalzen. Die letztgenannte Verbindung -weist pharmakologische Wirkung auf, und zwar besitzt sie eine decarboxylasehemmende Wirkung, wobei von besonderem Interesse ist, daß sie in Kombination mit L-Dopa hervorragende Mittel zur Behandlung von Parkinsonismus darstellt und antidepressiv wirkt Zum Nachweis der Überlegenheit wurden die von L-Dopa induzierten Erhöhungen von Catecholaminen (CA) im Gehirn durch Verwendung vonThe compounds according to the invention are intermediate compounds for the preparation of Ni-L-seryl-N 2 - (2,3,4-trihydroxy-benzyl) hydrazide and its acid addition salts. The last-mentioned compound has a pharmacological effect, namely it has a decarboxylase-inhibiting effect, it being of particular interest that, in combination with L-dopa, it is an excellent agent for the treatment of Parkinsonism and has an antidepressant effect. Dopa induced increases in catecholamines (CA) in the brain through the use of

1. 12 mg/kg Ni-D,L-Serin-N2-(2,3,4-trihydroxybenzyl)-hydrazid-hydrochlorid, Produkt des Beispiels 3 der deutschen Patentschrift 11 65 607 (Verbindung E in der nachstehenden Tabelle),1. 12 mg / kg Ni-D, L-serine-N 2 - (2,3,4-trihydroxybenzyl) hydrazide hydrochloride, product of Example 3 of German Patent 11 65 607 (compound E in the table below),

2. einer äquimolaren Menge von Ni-D,L-Alanin-N2-(2,3,4-trihydroxybenzyl)-hydrazid-hydrochlorid, Produkt des Beispiels 6 derselben Patentschrift (Verbindung F), und2. an equimolar amount of Ni-D, L-alanine-N2- (2,3,4-trihydroxybenzyl) hydrazide hydrochloride, Product of Example 6 of the same patent specification (compound F), and

3535

40 Verbindung
E F 40 connection
EF

Erhöhung von CA in
arbiträren EinheitenIncrease in CA in
arbitrary units

100100

11,5 13611.5 136

Daraus ergibt sich, daß die Verbindung G eine größere decarboxylasehemmende Wirkung hat als die bekannten Verbindungen E und F.As a result, Compound G has a greater decarboxylase-inhibiting effect than that known compounds E and F.

Die erfindungsgemäße Verbindung der Formel I und deren Salze können nach an sich bekannten Methoden erhalten werden, beispielsweise durch Umsetzung eines Säureadditionssalzes von L-Serinhydrazid mit 2,3,4-Trihydroxy-benzaldehyd. The compound of the formula I according to the invention and its salts can be prepared by methods known per se be obtained, for example by reacting an acid addition salt of L-serine hydrazide with 2,3,4-trihydroxy-benzaldehyde.

Die erfindungsgemäße Verbindung der Formel I kann durch katalytische Hydrierung in das pharmakologisch aktive N i-L-Seryl-N2-(2,3,4-trihydroxybenzyl)-hydrazid übergeführt werden.The compound of the formula I according to the invention can be converted into the pharmacologically active N iL-seryl-N 2 - (2,3,4-trihydroxybenzyl) hydrazide by catalytic hydrogenation.

Beispielexample

Herstellung von N|-L-Seryl-N2-(2,3,4-trihydroxybenzyliden)-hydrazid-hydrochlorid Preparation of N | -L-Seryl-N 2 - (2,3,4-trihydroxybenzylidene) hydrazide hydrochloride

15,4 g 2,3,4-TrihydroxybenzaIdehyd werden in 200 ml siedendem Wasser gelöst und auf einmal mit 15,2 g L-Serin-hydrazid-hydrochlorid versetzt Man erhält eine klare Lösung. Diese wird unter vermindertem Druck eingeengt und durch portionenweise Zugabe von Äthanol wird das Wasser allmählich verdrängt. Hierbei entsteht ein Kristallbrei. Dieser wird genutscht und mit Äthanol und Äther gewaschen. Man erhält das Ni-L-Seryl-N2-(2,3,4-trihydroxy-benzyliden)-hydrazidhydrochlorid vom F. = 260-265° C [a]D=+23° (C= 1;H2O).15.4 g of 2,3,4-trihydroxybenzaldehyde are dissolved in 200 ml of boiling water, and 15.2 g of L-serine hydrazide hydrochloride are added all at once. A clear solution is obtained. This is concentrated under reduced pressure and the water is gradually displaced by adding ethanol in portions. This creates a crystal pulp. This is sucked and washed with ethanol and ether. The Ni-L-Seryl-N 2 - (2,3,4-trihydroxy-benzylidene) hydrazide hydrochloride is obtained with a mp = 260-265 ° C [a] D = + 23 ° (C = 1; H 2 O ).

Claims (3)

Patentanspruch:Claim: Ni-L-Seryl-N2-(23,4-trihydroxy-benzyliden)-hydrazid und dessen Säureadditionssalze.Ni-L-Seryl-N 2 - (23,4-trihydroxy-benzylidene) hydrazide and its acid addition salts. 3. einer äqui*nolaren Menge des Ni-L-Serin-3. an equi * nolar amount of the Ni-L-serine N2-(£3.4-trihydroxybenzyl)-hydrazid-hydro-. chlorids (Verbindung G)N2- (£ 3.4-trihydroxybenzyl) hydrazide-hydro-. chlorides (compound G)
DE1966821A 1968-08-16 1969-08-13 Ni.i ^ »> i-N2 - (23.4-trihydroxy-benzylidene) hydrazide and its acid addition salts Expired DE1966821C3 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CH1240368A CH554844A (en) 1968-08-16 1968-08-16 METHOD OF MANUFACTURING A HYDRAZIDE.

Publications (3)

Publication Number Publication Date
DE1966821A1 DE1966821A1 (en) 1974-07-11
DE1966821B2 DE1966821B2 (en) 1978-03-16
DE1966821C3 true DE1966821C3 (en) 1978-11-23

Family

ID=4382677

Family Applications (2)

Application Number Title Priority Date Filing Date
DE1966821A Expired DE1966821C3 (en) 1968-08-16 1969-08-13 Ni.i ^ »> i-N2 - (23.4-trihydroxy-benzylidene) hydrazide and its acid addition salts
DE1941284A Expired DE1941284C3 (en) 1968-08-16 1969-08-13 N to the power of 1-L-Seryl-N to the power of 2- (2,3,4trihydroxybenzyl) hydrazide, process for its preparation and its acid addition salts and pharmaceuticals containing them

Family Applications After (1)

Application Number Title Priority Date Filing Date
DE1941284A Expired DE1941284C3 (en) 1968-08-16 1969-08-13 N to the power of 1-L-Seryl-N to the power of 2- (2,3,4trihydroxybenzyl) hydrazide, process for its preparation and its acid addition salts and pharmaceuticals containing them

Country Status (16)

Country Link
JP (1) JPS5114501B1 (en)
AT (2) AT299158B (en)
BE (1) BE737420A (en)
CA (1) CA958418A (en)
CH (1) CH554844A (en)
CS (1) CS162689B2 (en)
DE (2) DE1966821C3 (en)
DK (1) DK126776B (en)
ES (1) ES370500A1 (en)
FR (2) FR2015792B1 (en)
GB (1) GB1250279A (en)
IE (1) IE33519B1 (en)
IL (1) IL32767A (en)
MY (1) MY7300018A (en)
NL (1) NL6912320A (en)
SE (1) SE378242B (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103951587A (en) * 2014-04-11 2014-07-30 浙江耐司康药业有限公司 Synthetic method for intermediate of benserazide hydrochloride
WO2015197909A1 (en) 2014-06-27 2015-12-30 Fermion Oy Process for the preparation of a crystalline polymorph of 2-amino-3-hydroxy-n'-(2,3,4-trihydroxybenzyl)propanehydrazide (benserazide) hydrochloride

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3065265A (en) * 1957-07-04 1962-11-20 Hoffmann La Roche Amino acid hydrazides

Also Published As

Publication number Publication date
DE1966821B2 (en) 1978-03-16
CS162689B2 (en) 1975-07-15
FR2104722A1 (en) 1972-04-21
IL32767A (en) 1973-01-30
IE33519B1 (en) 1974-07-24
NL6912320A (en) 1970-02-18
DE1941284A1 (en) 1970-02-19
GB1250279A (en) 1971-10-20
CH554844A (en) 1974-10-15
DK126776B (en) 1973-08-20
AT299158B (en) 1972-06-12
DE1941284B2 (en) 1974-05-30
DE1941284C3 (en) 1975-01-30
FR2015792A1 (en) 1970-04-30
FR2104722B1 (en) 1974-03-22
JPS5114501B1 (en) 1976-05-10
BE737420A (en) 1970-02-13
SE378242B (en) 1975-08-25
FR2015792B1 (en) 1973-08-10
IE33519L (en) 1970-02-16
CA958418A (en) 1974-11-26
ES370500A1 (en) 1971-04-16
AT299160B (en) 1972-06-12
DE1966821A1 (en) 1974-07-11
MY7300018A (en) 1973-12-31
IL32767A0 (en) 1969-11-12

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8339 Ceased/non-payment of the annual fee