NZ208118A - Diphenylazomethine derivatives containing an esterfied chain and pharmaceutical compositions - Google Patents
Diphenylazomethine derivatives containing an esterfied chain and pharmaceutical compositionsInfo
- Publication number
- NZ208118A NZ208118A NZ208118A NZ20811884A NZ208118A NZ 208118 A NZ208118 A NZ 208118A NZ 208118 A NZ208118 A NZ 208118A NZ 20811884 A NZ20811884 A NZ 20811884A NZ 208118 A NZ208118 A NZ 208118A
- Authority
- NZ
- New Zealand
- Prior art keywords
- group
- alkyl radical
- alkoxy
- radical
- chain
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/12—Radicals substituted by oxygen atoms
Abstract
1. Claims (for the contracting states : BE, CH, DE, FR, GB, IT, LI, LU, NL, SE) Diphenylazomethines containing an esterified chain and corresponding to the formula (I) see diagramm : EP0125975,P15,F1 in which X1 , X2 and X3 independently of one another each represent a hydrogen or halogen atom or a (C1-6 )alkyl radical, R represents a straight-chain or branched (C1-6 )alkyl radical, n represents an integer from 1 to 10 and R' represents a straight-chain or branched (C1-6 )alkyl radical, a (C3-6 )cycloalkyl(C1-4 )alkyl radical, a (C3-7 )cycloalkyl radical, a (C2-6 )alkenyl radical, a (C3-6 )alkynyl radical, a (C1-4 )alkoxy(C1-4 )alkyl radical, a hydroxy-(C1-4 )alkyl radical, a (C1-4 )alkoxy-[(C1-4 )alkoxy]m -(C1-4 )alkyl radical, in which m is an integer from 1 to 3, a (C1-4 )alkoxycarbonyl(C1-4 )alkyl radical, a tetrahydrofurylmethyl radical, a phenyl-(C1-4 )alkyl radical which can carry a halogen atom, or a (C1-4 )alkoxy radical. 1. Claim (for the contracting state AT) Process for the preparation of diphenylazomethines containing an esterified chain and corresponding to the formula (1) see diagramm : EP0125975,P17,F1 in which X1 , X2 and X3 independently of one another each represent a hydrogen or halogen atom or a (C1-6 )alkyl radical, R represents a straight-chain or branched (C1-6 )alkyl radical, n represents an integer from 1 to 10 and R' represents a straight-chain or branched (C1-6 )alkyl radical, a (C3-6 )cycloalkyl (C1-4 )alkyl radical, a (C3-7 )cycloalkyl radical, a (C2-6 )alkenyl radical, a (C3-6 )alkynyl radical, a (C1-4 )alkoxy-(C1-4 )alkyl radical, a hydroxy-(C1-4 )alkyl radical, a (C1-4 )alkoxy[(C1-4 )alkoxy]m -(C1-4 )alkyl radical, in which m is an integer from 1 to 3, a (C1-4 )alkoxy-carbonyl-(C1-4 )alkyl radical, a tetrahydrofurylmethyl radical, a phenyl-(C1-4 )alkyl radical which can carry a halogen atom, or a (C1-4 )alkoxy radical, process characterised in that either a benzophenone (II) see diagramm : EP0125975,P17,F2 is reacted with the hydrochloride of an ester of an omega-amino-alkanoic acid (III) H2 N-(CH2 )n -COOR', HCl or an acid (IV) see diagramm : EP0125975,P17,F3 is reacted with an alcohol R'OH (V) in the presence of carbonyldiimidazole, or an alkali metal salt of an acid (VI) see diagramm : EP0125975,P18,F1 is reacted with a compound R'Y (VII), in which Y represents a halogen atom or a labil group, such as mesyl or tosyl, the radicals X1 , X2 , X3 , n, R and R' having the meanings given above.
Description
New Zealand Paient Spedficaiion for Paient Number £08118
208O8
/%
Priority Date(s):
Ji- ^ ??
Complete Specification Filed: (?. Class: c.?.7. ^W/4.. (\&(&./&.
C.?M4?jJ.'A
Publication Date: .2 3 JAN 1987
P.O. Journal, No: .......
HO DRAWINGS
NEW ZEALAND PATENTS ACT, 1953
No.: Date:
COMPLETE SPECIFICATION
DIPENYLAZOMETHINES CONTAINING AN ESTERIFIED CHAIN, THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
o
K/We SYNTHELABO, a French Body Corporate of 58, rue de la Glaciere, 75621 Paris, France,
hereby declare the invention for which K / we pray that a patent may be granted to mX/us, and the method by which it is to be performed, to be particularly described in and by the following statement: -
(Followed by page
DESCRIPTION
DIPHENYLAZOMETHINBS CONTAINING AN ESTERIFIED CHAIN, THEIR
PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM The present invention relates to diphenylazomethines containing an esterified chain, their preparation and their use in therapy.
The diphenylazomethine compounds according to the invention are of the formula in which X^, X2 and X^r which may be the same or different,
each represent a hydrogen or halogen atom or a (C^_g) alkyl group, R represents a straight-chain or branched (C^_g) alkyl group, n represents an integer from 1 to 10 and R' represents a straight-chain or branched (Ct_g) alkyl group, a (C^_g) cycloalkyl alkyl group, a (C^_^) cycloalkyl group, a
(C2_g) alkenyl group, a (C^_g) alkynyl group, a alkoxy-(C^_^) alkyl group, a hydroxy-(C^_^)alkyl group, a (Cj__^J alkoxy-[(Cj_^) alkoxy] (C2_4 ) alkyl group, in which m is an integer from 1 to 3, a alkoxy-carbonyl-(C^_^) alkyl group, a tetrahydrofurylmethyl group or a phenyl-(C^) alkyl group which can carry a halogen atom or a (_4) alko^y^i^^^
R
(I)
X
3
group
208118
n o
Preferred compounds according to the invention are those of the formula
R
C=N-
X3
in which X^, X£ and X^> which may be the same or different, 10 each represent a hydrogen atom, a chlorine atom or a methyl, ethyl or propyl group, n represents 3, 4 or 5, R represents a methyl, ethyl, n-propyl or isobutyl group and R' represents a straight-chain or branched (C^_g) alkyl group or a cyclopropylmethyl, cyclopentylmethyl, cyclohexylmethyl, 15 allyl, hydroxyethyl, (ci_4) alkoxy-ethyl,
ethoxycarbonylmethyl, tetrahydrofuryl-methyl, (methoxy-2-ethoxy)-2-ethyl, [(methoxy-2-ethoxy)-2-ethoxy]-2-ethyl, cyclohexyl, cyclopentyl, benzyl, propargyl, methoxy-benzyl or iso-penten-2-yl group; in particular compounds in which X^, 20 X2 and X.^, which may be the same or different, each represent a hydrogen atom, a chlorine atom or a methyl group, n is 3, 4 or 5, R represents a methyl, ethyl or n-propyl group and R' represents a methyl, ethyl, propyl, allyl or ethoxyethyl group; and more particularly compounds which correspond to 25 the formula
208118
=N-(CH2)n-cO0R' X.
in which the symbols have the meanings given above; of these Latter compounds/ the compounds of choice are those for which X ^ is a chlorine atom, X2 is a chlorine atom or a methyl group and X^ is a hydrogen atom.
According to the invention, the compounds may be prepared by any one of the following three methods:
method A D
+
method B
H-N-(CHJ -COOR' , H CI
(hi)
-> (I;
l| ^II>
3
carbonyldi imidazole
'CH2)n-C00H + R'OH (IV) (v)
: I)
208118
- 4 —
» (I)
M = alkali metal
Y = halogen or a labile group, such as mesyl or tosy I.
According to method A, a ketone (II)
is reacted with the hydrochloride of an ester of an w-amino-alkanoic acid (III) in a solvent, such as an alco~ hoi (methanol or ethanol), at a temperature from 60 to 100°C.
According to method B, an acid (IV), described in NZ Patent Specif ications Nos 202519 and 206409,
is reacted with an alcohol R'OH (V) in the presence of carbonyldiimidazole in a solvent, such as tetrahydrofuran, at a temperature from 60 to 140°C.
According to method C , an alkali metal salt of the acid (VI), described in NZ Patent Specifications Nos •
202519 and 206409, is reacted with a compound R'Y
(VII) in a solvent, such as anhydrous dimethyl sulphoxide, in the presence of a base, such as triethy I amine, at a temperature from 50 to 150°C.
208118
v./'
The hydrochlorides of esters of w-amino-a Ikanoic acids (III) can be prepared from the w-amino-aIkanoic acid by reaction with the corresponding alcohol R'OH in the presence of SOC^.
The alcohols R'OH (V) and the compounds R'Y (VII)
^ are described in the Literature.
The Examples which follow iLlustrate the invention.
The structures of the compounds were confirmed by 10 microanalyses and IR( UV and NMR spectra.
E xamp Le 1. Ethyl 4-£C(5-ch10ro-2-hydroxy-3-n-propylphenyl)-(4-chlorophenyl)-methyleneDaminoj-butanoate (X1 = 5-Cl, X2 = 4-Cl, X3 = H, n = 3, R = n-C3H?/ R' = C2H5)
1. A suspension of 206 g (2 moles) of 4-aminobu-
tanoic acid and 1/200 cm' of ethanol is brought to 50-60°C in an oil bath/ while stirring. 252 ml of SOC 12 are added in the course of 1 hour, while bringing up and maintaining the mixture at the reflux temperature for 3 20 hours.
The mixture is evaporated to dryness and the residue is washed twice with 500 cm' of ether each time.
After purification of the solution of the residue in ethanol with the aid of vegetable charcoal and washing 25 with ether, white hygroscopic crystals are obtained. Melting point = 72°C.
2. A mixture of 6 g (0.0194 mole) of (5-chloro-
2031 1 ®
D
2-hydroxy-3-n-propy lphenyl)-(4-ch lorophenyD-methanone, 4.06 g (0.0242 mole) of the hydrochloride of ethyl 4-arii nobutanoate and 4.06 g (0.0483 mole) of sodium bicarbonate in 600 ml of ethanol is evaporated to dryness. The 5 reaction mixture is stirred under reduced pressure at 100°C for 15 minutes.
The mixture is then evaporated 3 times with 500 ml of ethanol each time. The residue is taken up in 300 ml of CH2ci2 and 200 ml of water, the reaction 10 mixture is decanted and the organic phase is separated off and dried over MgSO^. It is evaporated to dryness. The residue is purified over a silica column, the mixture being eluted with 2.5 litres of C H 2 C 12 .
The fractions are dried over MgSO^, filtered 15 and evaporated to dryness. The residue is crystallised from 50 ml of ether. The crystals are filtered off, drained and dried in a desiccator in the presence of p2o5.
Melting point = 57-58°C.
Examp le 2. Ethyl 5-(5-ch10ro-2-hydroxy-3-methy I -
' phenyl)-(4-chlorophenyl) methyleneDamino^-pentanoate.
CX1 = 5-Cl, X2 = 4-Cl, x3 = H, n = 4, R = CH3,
r' = c2h5:
g (0.0533 mole) of (5 - v. h I o ro-2-h y d r oxy-3-25 methy1pheny I)-(4-ch Ioropheny I)-methanone, 2.96 g (0.0547 mole) of sodium methylate and 6.25 g (0.0533 mole) of 5-aminopentanoic acid are introduced into a 1 litre flask.
\ 1
208118
400 ml of toluene and 100 ml of methanol are added, the mixture is heated progressively and the azeotrope formed is distilled off, and the mixture is then heated at the reflux temperature of toluene, using a Dean-Stark appara-5 tus, for 6 hours.
The mixture is evaporated to dryness, the residue is triturated in ether and the solid is filtered off. The solid is introduced into water and acidified to pH 4 with citric acid. The solid is filtered off, dissolved 10 in chloroform, dried over magnesium sulphate and evaporated. The compound is recrysta 11ised from a mixture of cyclohexane/benzene. The solid is dissolved again in methylene chloride and the solution is passed over a silica column, elution being carried out with methylene 15 chloride and with a mixture of methylene chloride/ethyl acetate 80/20. After evaporation, a solid is obtained, and is dried.
Melting point = 110-111°C.
g (0.0131 mole) Of 5-(5-ch loro-2-hydroxy-3-20 methylphenyl)-(4-chlorophenyl)-methylene3aminojpentanoi c acid, obtained above, are dissolved in 100 ml of tetrahy-drofuran. 3.5 g (0.0215 mole) of carbonyldiimidazole are then added and the reaction mixture is stirred at room temperature for one hour. A further 3.5 g (0.0215 25 mole) of carbonyIdiimidazo I e is added and stirring is continued for one hour. The mixture is evaporated to • dryness and the residue is taken up in 200 ml of ether
208118
and 200 ml of water; the reaction mixture is decanted, the organic phase is separated off and dried over M g S 0 ^ , the MgSO^ is filtered off and the filtrate is evaporated to dryness.
After addition of 30 ml of hexane to the residue,
the product crystallises.
After filtration and recrystaLlisation, the crystals are dried.
Melting point = 73-74°C.
ExampIe 3. CyclohexyLmethyL 4-(5-chloro-2-hy-
droxy-3-methylphenyl)-(4-chlorophenyl) methylene]aminoj> -butanoate.
CX-, =5-C I, X2=4-Cl, X3=H, n=3, R = CH3, R' = ^ CH_-]
2.5 ml of cyclohexyLmethyL bromide (d=1.27, that 15 is to say 0.018 mole) and 2 drops of triethylamine are added to 5.8 g (0.015 mole) of the sodium salt of 4-£[(5-chloro-2-hydroxy-3-methylphenyl)-(4-chlorophenyl) met h y-leneUaminoj-butanoic acid in 100 ml of anhydrous dimethyl sulphoxide; the reaction mixture is heated at 100°C 20 for 4 hours, while stirring. The dimethyl sulphoxide is then evaporated off in vacuo and the residue is partitioned between 100 ml of ether and 100 ml of water. The mixture is decanted, the ethereal phase is dried over MgSO^ and filtered and the filtrate is evapora-25 ted to dryness. An oil is obtained, which crystallises in 40 ml of pentane. The crystals are filtered off,
washed with 10 ml of pentane, drained and dried in a
n
<>081 18
desiccator, whilst being heated at 40 , in the presence of P2^5 ■
Melting point = 53-54°c.
1
2
3
4
6
7
8
9
11
12
13
14
16
Table
208118
C=N-(CH-) -COOR' £ n
X1
X2
X3
R
R'
n lelting Point (°C) or nD
-C1
4-Cl
H
<*3
3
n2°=l- 5889
-C1
3-CH3
H
<*3
<*3
3
m-P»64-65
-C1
4-Cl h
n-C3H7
ch3
3
n21D5=l-5820
-C1
h h
^3
3
m-p*=73-74
-CH3
4-Cl
H
^3
3
"•P =6 3-64
-C1
4-Cl
H
<2*5
3
m.p ^52-53
-C1
4-CH3
H
(gh3)2-ch-ffl2-
®3
3
n22' 5=1-5669
-C1
4-C2h5
H
C w 2"5
ffi3
3
n2*«l-5756
-C1
4-Cl
H
C,3
3
m-p-=—82—83
-C1
4-Cl h
^3
c2h5
1
»-P«=108-109
-C1
4-Cl
H
nc4h9
3
m-p >=53-54
-C1
4-CH3
»
<*3
ch3
3
n2p=l-5884
-C1
4-Cl
H
ffl3
®3
2
"•p-72-73
-C1
4-Cl h
n-C3H?
C2H5
3
™>.p -=57-58
-C1
4-Cl h
<*3
3
22- 5 Hp =1-6064
-C1
3-CH3
H
<*3
C2H5
3
n2p=l•5300
-C1
4-Cl
H
ch3
C2H5
4
™-P =73-74
I- ' " -V I i. • ,
n
Table (continuation 1)
Compound
X1
X2
X3
R
R'
n
Melting point (°C) or
18
-Cl
4-Cl
H
®3
CT3
1
■ • P- =133-134
19
-Cl
4-Cl
H
<*3
tC^Lj
3
m. p. -=54-56
21
-Cl 5-Cl
4-Cl 4-Cl
E H
®3
CH2-CH=CH2
m3
3
4
m. p. =57-58 ■-P- =61-62
22
-CH3
4-Cl
H
: ®3
^5
3
m. P. =52-53
23
-Cl
4-Cl
H
QI3
m3
m. p. =39-40
24
-Cl 5-Cl
4-Cl 4-Cl
H H
. ^3
m3
C2H5
0^2
2
3
m. P.=55—56 m.p. =53—54
26
-Cl
4-Cl
H
nC3H7
ffi3
2
m-p.-59_70
27
-Cl
4-Cl
H
rC^n c2h5
2
m.p. =71-72
28
-Cl
4-Cl
H •
^3
nCjHn
3
n21D5=l. 5669
29
-Cl
4-Cl
H.
<=3
C2H5
»-p- =34-35
-Cl
4-CH3
H
(CH3) 2-C-:-C-:2
<7*5
3
n2*=l-5609
31
-Cl
4-C2h5
H
C2H5
C2H5
3
n2J=l- 5669
32
33
-Cl 5-Cl
4-Cl 4-Cl
H H
CT3 <*3
O^O^CH
CH2CH2OCH2CH3
3 3
».P. =74-75 «. p. =35-36
34
-Cl 5-Cl
4-Cl 4-Cl
H H
^3
CH2CH2OCH3
al2ai2OC4Hg
3 3
».p. =34-35 n2J 5=15643
36
-Cl
4-CH3
H
®3
C2H5
3
n.P- -57-58
37
38
-Cl 5-Cl
4-Cl 4-Cl
H H
<*3 <*3
m2-OOOC2H5
3 3
22
n £=1-5700
n.p. =77-78
39
40
-Cl 5-Cl
4-Cl 4-Cl
H
<*3 ®3
Eai2)2-°3-2CH3
X)
3 3
»-p- =30-21 n.D. =76-77
?08118
Table (continuation 2)
Compound
X1
X2
X3
b r'
n
Melting point (°C) or nD
41
-Cl
4-CH3
2-CH3
ch3
c2h5
3
n20"5=1-5743
42
-Cl
4-Cl h
ch3
ca*l2)
3
"B1" 15575
43
-Cl
4-Cl h
ch3
-Cl
3
m-p-85 95-96
44
-Cl
4-CH3
h nC3H?
^3
3
n21' 5=1- 5774
45
-Cl
4-Cl h
nC3H?
ch3
4
64-65
46
-Cl
4-Cl h
nC3H?
C2H5
4
n.p.s 41-42
47
-Cl
4-Cl h
nc3h?
CH3
m.p.ss 40-41
48
-^3
4-ch3
2-CH3
ch3
ch3
3
n23= 1-5710
49
-Cl
4-Cl h
nc3h?
c2h5
n23= 1-5663 d
50
-Cl
4-Cl h
ch3
ra2-0
3
m.p.= 101-102
51
-Cl
4-CH3
2-CH3
ch3
ch3
3
23
= 1-5770
52
-Cl
4-Cl h
ch3
ch2-0
3
n.p.= 102-103
53
-Cl
4-Cl h
ch3
-CH2C=CH
3
™.d.= 70-71
54
-CH3
4-nC3H7
H
C2H5
CBj
3
n2l= 1-5610
55
-Cl
4-Cl h
ch3
i-cjh?
3
n2l= 1-5751
56
-CH3
4-Cl
2-CH3
ch3
ch3
3
n22"5=1-5810
57
-Cl
4-Cl
H
ch3
-CH ^ ^2*5
3
n2l = 1 -5725
Table (continuation 3)
1
Comp ound
X1
*3
R
R'
n
Melting point t°C) or nn
58
-Cl
4-Cl
H
^3
(CH^CH^O) 3CH3
3
23
n 3=1-5559
59
-Cl
4-Cl
H
ffi3
3
m-p«58-59
60
-Cl
4-Cl
H
<*3
uCHj
®3
7
1 • p <=39—40
61
-Cl
4-Cl
H
"3
6
"3—38-39
62
-Cl
4-Cl
H
®3
OL-CHsC^3
3
n2J=J- 5751
63
-Cl
4-Cl
H
ffi3
1C4H9
3
n-P.=84-85
64
-Cl
4-Cl
H
<*3
®3
8
»-p -=37-38
65
-Cl
4-CL
H
ch3
GH3
9
"•p-=54-55
66
-Cl
4-Cl
H
nC^Lj
CH2Oi2OC^s
3
n2p=l - 5663
67
-Cl
4-Cl
H
^3
a3
m.Pe39_40
68
-Cl
4-Cl
H
nC3H7
(CH2)2OCH3
4
n*D 5=1- 5654
69
-Cl
4-Cl
H
nC3H?
(CH^20-C2H5
4
24 5 n p' =1. 5620
70
-Cl
4-Cl
H
nCjB,
CH2-CH=CH2
4
-36
71
-Cl
4-Cl
H
nCjH,
(CH2)2OC2H5
n2®'5=l-5554
72
-Cl
4-CH3
H
nCjB,
<*3
4
73-74
73
-Cl
4-Cl
H
nC3H?
(CH2)2OCH3
n2p 5=1-5634
74
-Cl
4-CH3
H
nC3H7
C2H5
4
62-63
\
8
\ 18
Table (continuation O
Compound
*1
*2
x3
r r'
n
Melting point (°C) or nQ
75
-Cl
4-Cl h
nC3H?
iC^
4
55-56
76
-Cl
4-CH3
h
C2H5
3
n^4=l-5635
77
-Cl
4-Cl h
®3
(CH2)2OC2H5
n^°=l- 5558
78
-Cl
4-Cl h
<*3
ch(ch3)ch2och3
3
55-56
79
-Cl
4-CH3
h nc3h7
®3
31-32
80
-Cl
4-Cl h
ch3
(CH2)2OC2H5
4
n£6=l. 5600
81
-Cl
4-Cl h
CH3
(CH2)3OC2H5
3
n^8=l-5650
82
-Cl
4-Cl h
<*3
(CH2)2CH(OCH3)-CH3
3
n^8=l•5653
83
-Cl
4-CH3
h nC3H?
(ch2)2oc2h5
4
n^3=l•5042
84
-Cl
4-Cl h
CT3
CH2COCH3
3
78-2
85
-Cl
4-ch3
h ra3
<*3
4
70-71
86
-Cl
4-CH3
h
<*3
^3 . .
40-41
87
-Cl
4-C2h5
h c2«5
<*3
n^3=l.5693
88
-Cl
4"C2H5
h
C2H5
<*3
4
23
n£ =1.5722
89
-Cl
4-Cl h
C2H5
m3
4
70-71
90
-Cl
4-Cl h
C2H5
ffi3
n^XL.5799
2'CffrV
The compounds according to the invention have been subjected to pharmacological tests demonstrating their activity on the central nervous system.
The acute toxicity was determined on mice by oral administration. The LDjq (50% lethal dose) which causes the death of 50% of the animals is greater than 1,000 mg/kg.
The anticonvulsive activity of the compounds was demonstrated by antagonism of the mortality induced by bicuculline in mice.
Bicuculline is a relatively selective blocker of post-synaptic GABA-ergic receptors and its convulsive and lethal effects are antagonised by compounds which increase the level of cerebral GABA or have a GABA-mimetic activity.
The 50% active dose (ADjg), that is to say the dose which protects 50% of the animals from the effect of bicuculline, of the substances studied was evaluated.
The AD50 on oral administration of the compounds according to the invention varies from 10 to 200 mg/kg.
The compounds according to the invention are active as anticonvulsants and also have antidepressive, anxiolytic, analgesic, antiinflammatory, antiulcerous and antidyskinetic properties. They can be used in human and veterinary therapy, inter alia for the treatment of various diseases of the central nervous system, for example for the treatment of depression, psychoses and certain
2081 18
neurological diseases, such as epilepsy, spasticity and dyskinesia.
The invention accordingly relates to all pharmaceutical compositions containing the compounds (I) as a c-5 tive principles, together with any excipients suitable for their administration, in particular oral (tablets, coated tablets, gelatin capsules, capsules, cachets and solutions or suspensions for oral use) or parenteral administration.
The daily posology may be from 100 to 4,000 mg.
,/
?' ••
■ ■
2081X8
17
Claims (9)
1. A diphenylazomethine containing an esterified chain and corresponding to the formula (I) in which XX2 and X3, which may be the same or different, each represent a hydrogen or halogen atom or a (C1_g) alkyl group, R represents a straight-chain or branched (C1_g) alkyl group, n represents an integer from 1 to 10 and R' represents a straight-chain or branched (Cj.g) alkyl group, a (C3_g) cycloalkyl—(C1-4) alkyl group, a cycloalkyl group, a (C2_6) alkenyl group, a (C3_6) alkynyl group, a <C1_4) alkoxy-(C1_4) alkyl group, a hydroxy-(Cj_4)alkyl group, a (C^Jalkoxy-fc^Jalkoxy] -(C^J alkyl group in which m is an integer from 1 to 3, a alkoxy-carbony1-(C^_4) alkyl group, a tetrahydrof urylmethyl group or a phenyl-fC^) alkyl group which can carry a halogen atom or a (c^_4) alkoxy group. R 20^1^ ® 18
2. A compound according to claim 1, wherein X^, X2 and X^, which may be the same or different, each represent a hydrogen atom, a chlorine atom or a methyl, ethyl or propyl group, n represents 3, 4 or 5, R represents a methyl, ethyl, n-propyl or isobutyl group and R1 represents a straight-chain or branched (C^_g) alkyl group or a cyclopropylmethyl, cyclopentylmethyl, cyclohexylmethyl, allyl, hydroxyethyl, {C^_4) alkoxy-ethyl, ethoxycarbonylmethyl, tetrahydrofuryl-methyl, (methoxy-2-ethoxy)-2-ethyl, [ (methoxy-2-ethoxy)-2-ethoxy]-2-ethyl, cyclohexyl, cyclopentyl, benzyl, propargyl, methoxy-benzyl or iso-penten-2-yl group.
3. A compound according to claim 2, in which X^, X2 and which may be the same or different, each represent a hydrogen atom, a chlorine atom or a methyl group, n is 3, 4 or 5, R represents a methyl, ethyl or n-propyl group and R' represents a methyl, ethyl, propyl, allyl or ethoxyethyl group.
4. A compound according to claim 3, corresponding to the formula R A J -V I o 08^ 18 - 19 - in which the various symbols are as defined in claim 3.
5. A compound according to claim 4, in which is a chlorine atom, X2 is a chlorine atom or a methyl group, X^ is a hydrogen atom, and n, R and R' are as defined in claim 3.
6. A diphenylazomethine according to claim 1 substantially as described with reference to any one of Examples 1 to 90 in the Table.
7. A process for the preparation of a diphenylazomethine as claimed in any one of claims 1 to 6, wherein (i) a benzophenone of the formula (II) R (II) 'W is reacted with the hydrochloride of an ester of anO-amino- alkanoic acid of the formula (III) H2N-(CH2)n-C00R',HC1 (III); or (ii) an acid of the formula (IV) R =N-(CH,) -C00H 4 n (IV) 20^\ IS 20 is reacted with an alcohol R'OH (V) in the presence of carbonyldiimidazole; or (iii) an alkali metal salt of an acid (VI) in which M represents an alkali metal is reacted with a compound R'Y (VII ), in which Y represents a halogen atom or a labile group, the symbols X^, *3 > n' R an<* Rl being as defined in any one of claims 1 to 5.
8. A process according to claim 7 substantially as described with reference to Example 1, 2 or 3.
9. A pharmaceutical composition which comprises as active ingredient at least one compound as claimed in any one of claims 1 to 6, together with a pharmaceutical^ acceptable excipient. r (vi) Jl/JjJULuiLsrYl^)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR8307863A FR2545822B1 (en) | 1983-05-11 | 1983-05-11 | DIPHENYLAZOMETHINES CARRYING AN ESTERIFIED CHAIN, THEIR PREPARATION AND THEIR APPLICATION IN THERAPEUTICS |
Publications (1)
Publication Number | Publication Date |
---|---|
NZ208118A true NZ208118A (en) | 1987-01-23 |
Family
ID=9288787
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NZ208118A NZ208118A (en) | 1983-05-11 | 1984-05-10 | Diphenylazomethine derivatives containing an esterfied chain and pharmaceutical compositions |
Country Status (16)
Country | Link |
---|---|
EP (1) | EP0125975B1 (en) |
JP (1) | JPS59212458A (en) |
AT (1) | ATE18760T1 (en) |
AU (1) | AU2788584A (en) |
DE (1) | DE3460059D1 (en) |
DK (1) | DK232084A (en) |
ES (1) | ES532363A0 (en) |
FI (1) | FI841882A (en) |
FR (1) | FR2545822B1 (en) |
GR (1) | GR82093B (en) |
HU (1) | HU191652B (en) |
IL (1) | IL71796A0 (en) |
NO (1) | NO841878L (en) |
NZ (1) | NZ208118A (en) |
PT (1) | PT78575A (en) |
ZA (1) | ZA843545B (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007127440A2 (en) * | 2006-04-27 | 2007-11-08 | Intezyne Technologies, Inc. | Heterofunctional poly(ethylene glycol) containing acid-labile amino protecting groups and uses thereof |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2319338A1 (en) * | 1975-08-01 | 1977-02-25 | Synthelabo | NEW A-PHENYL BENZYLIDENIC DERIVATIVES OF AMINO ACIDS, THEIR PREPARATION AND THE MEDICINAL PRODUCTS CONTAINING THEM |
-
1983
- 1983-05-11 FR FR8307863A patent/FR2545822B1/en not_active Expired
-
1984
- 1984-05-02 EP EP84400889A patent/EP0125975B1/en not_active Expired
- 1984-05-02 AT AT84400889T patent/ATE18760T1/en not_active IP Right Cessation
- 1984-05-02 DE DE8484400889T patent/DE3460059D1/en not_active Expired
- 1984-05-10 DK DK232084A patent/DK232084A/en not_active Application Discontinuation
- 1984-05-10 ES ES532363A patent/ES532363A0/en active Granted
- 1984-05-10 PT PT78575A patent/PT78575A/en unknown
- 1984-05-10 AU AU27885/84A patent/AU2788584A/en not_active Abandoned
- 1984-05-10 IL IL71796A patent/IL71796A0/en unknown
- 1984-05-10 NZ NZ208118A patent/NZ208118A/en unknown
- 1984-05-10 NO NO841878A patent/NO841878L/en unknown
- 1984-05-10 ZA ZA843545A patent/ZA843545B/en unknown
- 1984-05-10 FI FI841882A patent/FI841882A/en not_active Application Discontinuation
- 1984-05-10 HU HU841829A patent/HU191652B/en unknown
- 1984-05-10 JP JP59094420A patent/JPS59212458A/en active Pending
- 1984-05-10 GR GR74674A patent/GR82093B/el unknown
Also Published As
Publication number | Publication date |
---|---|
PT78575A (en) | 1984-06-01 |
FI841882A0 (en) | 1984-05-10 |
EP0125975A1 (en) | 1984-11-21 |
JPS59212458A (en) | 1984-12-01 |
ZA843545B (en) | 1984-12-24 |
NO841878L (en) | 1984-11-12 |
IL71796A0 (en) | 1984-09-30 |
GR82093B (en) | 1984-12-13 |
HUT34436A (en) | 1985-03-28 |
ES8502678A1 (en) | 1985-01-16 |
ATE18760T1 (en) | 1986-04-15 |
EP0125975B1 (en) | 1986-03-26 |
DK232084D0 (en) | 1984-05-10 |
HU191652B (en) | 1987-03-30 |
AU2788584A (en) | 1984-11-15 |
DE3460059D1 (en) | 1986-04-30 |
FI841882A (en) | 1984-11-12 |
FR2545822B1 (en) | 1985-07-05 |
FR2545822A1 (en) | 1984-11-16 |
DK232084A (en) | 1984-11-12 |
ES532363A0 (en) | 1985-01-16 |
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