DD201900A5 - PROCESS FOR PREPARING C-3 NUCLEARED 1,4-DIHYDROPYRIDINES - Google Patents

Abstract

1. 1,4-Dihydropyridines which are linked in the C-3 position, of the general formula I see diagramm : EP0052300,P19,F4 in which R and R' are identical or different and each represent a phenyl radical or a thienyl, furyl, or pyridyl radical, the phenyl radical is optionally substituted by one or two identical or different substituents from the group comprising nitro, cyano, azido, halogen, trifluoromethyl, hydroxyl, amino, alkyl, alkoxy, alkylamino or alkylmercapto, with in each case 1 or 2 carbon atoms in the alkyl groups, R**1 and R**1' are identical or different and each represent a straight-chain or branched hydrocarbon radical having up to 6 carbon atoms which is optionally interrupted in the chain by an oxygen atom and which is optionally substituted by fluorine, chlorine, hydroxyl, phenyl or phenoxy, R**2 , R**2' , R**4 and R**4' are identical or different and each represent hydrogen or a straight-chain or branched alkyl radical which has up to 4 carbon atoms and which is optionally substituted by fluorine, chlorine, hydroxyl, phenyl or amino, R**3 and R**3' are identical or different and each represent hydrogen, alkyl having 1 to 4 carbon atoms, phenyl, benzyl or phenethyl, optionally substituted by hydroxyl, fluorine or chlorine, Y and Y' are in each case identical or different and each denote - COO -, - CONH -, - CO - or - SO2 - and X denotes a bridge member which consists of one to ten CH2 groups as the chain member, and none of these CH2 groups are allowed as a ring member, it being possible for this bridge member additionally to contain, in any sequence, 1 to 3 identical or different chain members from the group comprising O, S, CO, CS, NR**5 , C(R**6 )2 , CH = N, phenylene, naphthylene, pyrrylene, cycloalkylene with 5 to 7 carbon atoms, piperazinylene, piperidinylene, pyrrolidinylene or morpholinylene, wherein R**5 represents hydrogen, benzyl or alkyl having 1 to 4 carbon atoms and R**6 represents hydrogen, benzyl, phenyl, fluorine, chlorine, alkyl having 1 to 4 carbon atoms, hydroxyl, trifluoromethyl, cyano, carboxyl or amino and their pharmacologically acceptable acid addition salts.

Description

59 702/11

Process for the preparation of C-3 linked 1,4-dihydropyridines

Field of application of the invention

The present invention relates to processes for the preparation of novel dimeric "4-dihydropyridines, which are linked together in the 3-position and their use in medicaments, in particular in medicaments with a circulation-influencing action,

Characteristic of the known technical solutions

It is already known that certain 1,4-dihydropyridine derivatives have interesting pharmacological properties (cf., F * Bessert et al., Naturwissenschaften 5J3, 578 (1971) and DE-OS 2 117 571).

Object of the invention

The aim of the invention is the provision of new circulation-influencing, in particular antihypertensive agents,

Presentation of the essence the invention

The invention has for its object to find new compounds with the desired properties and processes for their preparation.

-7, FTE! * 1,982 OOeSö2

234 7

-Ia-

4 * 5.1982

AP C 07 D / 234 718/0

59 702/11

According to the invention, new C-3 linked 1,4-dihydropyridines of the general formula (I)

R ¹ OOC

COOR

(1)

manufactured,

3 4,718 O

in which

R and R 'are the same or different and each represents an aryl radical or a thienyl, furyl, pyrryl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, pyridyl, pyridazinyl,

Pyrimidyl, pyrazinyl, naphthyl, quinolyl, isoquinolyl, indolyl, benzimidazolyl, quinazolyl or quinoxalyl, wherein the aryl radical and the heterocycles optionally have 1 to 3 identical or different substituents

the group phenyl, alkyl, alkenyl, alkoxy, alkenoxy, alkylene, dioxyalkylene, halogen, monofluoroalkyl, polyfluoroalkyl, monofluoroalkoxy, polyfluoroalkoxy, hydroxy, amino, alkylamino, nitro, cyano, azido, carboxy, carbalkoxy, car-

bonamido, sulfonamido or SO-alkyl (m = 0

m ~

to 2),.

11 'R and R are the same or different and each one

straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon

represent rest, which is optionally interrupted by 1 or 2 oxygen atoms in the chain, and which is optionally substituted by halogen, hydroxy or by a.- phenyl, phenoxy, phenylthio or Phe

nyl sulfonyl group, which in turn may be substituted by halogen, cyano, dialkylamino, alkoxy, alkyl, trifluoromethyl or nitro,

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2 '4 4'

R, R, R 'and R' are the same or different and each represents hydrogen, a straight-chain or branched, cyclic, saturated or unsaturated hydrocarbon radical which is optionally substituted by halogen,

Hydroxy, aryl or amino or an amino group, which in turn may optionally be substituted by a hydrocarbon radical, said hydrocarbon radical "Ό straight-chain, branched, cyclic, saturated

or may be unsaturated and is itself optionally substituted,

3 '

R and R are the same or different and each for

Hydrogen or an optionally substituted

5 substituted straight-chain or branched alkyl

rest, which is optionally interrupted by one or two oxygen atoms in the alkyl chain or are an optionally substituted aryl or aralkyl radical, γ and Y 'are each the same or different and each have the meaning. ·

0 0 0 0 -CO-, -C-NH-, -CS-, -C- or -SO ₂ -

have and

X for a bridge member with at least one CH_ group and at most 9 adjacent CH groups

stands, this bridge member additionally in any order 1 to 5 identical or different chain links from the group

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-ΊΟ, S, SO, -SO ₂ , CO, CS, NR ⁵ , C (R ⁶ ) ₂ , CR ⁶ = CR ⁶ , C =C, CH =N, arylene, heteroarylene, cycloalkylene, cycloalkenylene, piperazinylene, piperidylene , Pyrrolidinylene or morpholinylene, wherein

R is hydrogen, alkyl or aralkyl and

R is hydrogen, aralkyl, aryl, heteroaryl, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, IQ alkynoxy, alkylene, dioxyalkylene, halogen,

  Monofluoroalkyl, polyfluoroalkyl, monofluoroalkoxy, polyfluoroalkoxy, hydroxy, amino, alkylarnino, nitro, cyano, azido, carboxy, carb

alkoxy, carbonamido, sulfonamido or SO -

·] 5 alkyl (m = 0 to 2) and in theirs

on the one hand the aryl, alkyl and heteroaryl radicals can be substituted by one to three identical or different radicals from the group aryl, alkyl,. alkoxy, aralkyl, dioxyalkylene, halogen, monofluoroalkyl, polyfluoroalkyl, mono-

fluoroalkoxy, polyfluoroalkoxy, hydroxy, amino, alkylamino, nitro, cyano, acido, carboxy, carb

alkoxy, carbonamido, sulfonamido or SO -

Alkyl (m = 0 to 2),

and their pharmacologically acceptable acid addition salts.

The compounds of the general formula (I) according to the invention can be obtained by reacting

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A) 1,4-dihydropyridine hydroxy derivatives of the general formula (II)

R ¹ OOC 1 YX-OH

R ²

R ³

in which

12, R, R, R, R, R, Y and X are as defined above

to have,

in an inert organic solvent in the presence of water-binding agents with dihydropyridine-3-carboxylic acid derivatives of the general formula (III)

^ 'xjLcOOR ¹ ' ..

Ii ¹ L 2 ' ^(III)

, ^R R ³ '

in which

R ¹ , R, R, R, R and Y 'have the abovementioned meaning, where Y' is not a carbonyl group,

5 in equivalent amounts with elimination of water at temperatures between ο ⁰ C and 18O ° C, or

B) 1/4-dihydropyridinecarboxylic acids of the general formula (IV)

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- 6 RR ¹ OOC .L COOH

PU

R ³

in which

12 3 4 R, R, R, R and R have the abovementioned meaning,

in the presence of an inert organic solvent and optionally in the presence of a condensing agent with a bifunctional compound of the general formula (V)

Z-X-Z '(V)

in which X has the meaning given above and

Z and Z 'are each the same or different and are hydroxyl, mercapto or the radical NR, where R ^{D has} the abovementioned meaning,

in a molar ratio of about 2: 1 at temperatures between 0 ⁰ C and 180 ⁰ C, whereby according to this variant, only compounds of the general formula (I) are obtained in -denen Y and Y ¹ not for a carbonyl group. stand, or

C) Yliden-β-ketoesters of the general formula (VI)

R-CH = CCT ₁ (VI)

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12 R, R and R have the abovementioned meaning,

with enaminocarboxylic esters of the general formula (VI-I)

R ⁴ -C = CH-YX-Y'-CS = CR ⁴ '' (VII)

R NH HNR

in which, R ⁴ , 1 have,

3 3 '4 4' R, R, R, R ', Y and Y' are as defined above

in the presence of inert organic solvents in molar ratios of about 2: 1 at temperatures between ^{0 0} C and 180 ⁰ C.

According to this process variant C) it is possible to use symmetrical compounds, i. Connections in

3 3 '4 4'

each of which Y and Y ', R and R and R * and R * are identical, produce. According to this process variant C) it is also possible to prepare symmetrical compounds of the general formula (I) in which Y is a carbonyl group. -

The dihydropyridines of the general formula (I) according to the invention possess valuable pharmacological properties. Due to their effect on the circulation they can be used as antihypertensive agents, as vasodilators, as cerebral therapeutics and as coronary therapeutics. Surprisingly, they show particularly long-lasting effects and are thus regarded as an enrichment of pharmacy.

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Of particular interest are compounds of the general formula (I) according to the invention in which

R and R ^{1 represent} a phenyl or naphthyl radical or a thienyl, furyl, .pyryl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, pyridyl, pyridazinyl, pyrimidyl, pyrazinyl, Quinolyl, isoquinolyl, indolyl, benzimidazolyl, quinazolyl or quinoxalyl, where these aryl or heterocyclic groups are optionally 1 or 2, same or different

• 10 substituents from the group phenyl, alkyl having 1 to 8 carbon atoms, cycloalkyl having 3 to 7 carbon atoms, alkenyl or alkynyl each having 2 to 6 carbon atoms, alkoxy,. Alkenoxy or alkynoxy each having up to 4 carbon atoms, alkylene chain having 3 to 6 carbon atoms, dioxyalkylene having 1 or 2 carbon atoms, halogen, trifluoromethyl, trifluoromethoxy, difluoromethoxy, tetrafluoroethoxy, nitro, cyano, azido, hydroxy, amino, mono- and dialkylamino each with 1 to 4 C atoms per alkyl group, carboxy, carbalkoxy having in each case 2 to 4 C atoms, carbonamido, sulfonamido, sulfonalkyl or alkylmercapto · having in each case 1 to 4 carbon atoms per alkyl radical; "

1 'R and R are the same or different and each represents a straight-chain, branched, cyclic, saturated or unsaturated hydrocarbon radical having up to 8 Kohlenstoftatomen which is optionally interrupted by 1 or 2 oxygen atoms in the chain and which is optionally substituted by Fluorine, chlorine, hydroxyl, phenyl, phenoxy, phenylthio or phenyl

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.nylsulfonyl, wcbei the Phenylreste'hrseits are optionally substituted by 1 or 2 identical or different substituents from the group nitro, trifluoromethyl, cyano, fluorine, chlorine, alkyl or dialkylamino having in each case 1 to 4 carbon atoms in the alkyl radicals;

2 7 '4 4'

R, R ", R * and R are the same or different and are each hydrogen, a straight-chain, branched, cyclic, saturated or unsaturated hydrocarbon radical having up to 8 carbon atoms, which in turn is optionally substituted by fluorine, chlorine, hydroxyl, phenyl , Amino, 'alkylamino or cycloalkyl having up to 6 carbon atoms,

3 3 '

R and R are the same or different and each represents hydrogen or a straight-chain or branched alkyl radical having up to 8 carbon atoms, optionally interrupted by an oxygen atom in the chain or substituted by hydroxyl or halogen, or a phenyl, benzyl -. or phenethyl radical,

γ and Y ^{1 are} each the same or different and each have the meaning -COO-, -CONH-, -CO-, -COS- or -SO 2 -, and '

X stands for a bridge member having at least one non-ring bound CH ₂ ~ group and at most 9 adjacent CH ₂ ~ groups as chain links, wherein the bridge member additionally in any order 1 to 4 identical or different chain links

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the group O, S, SO ₂ , CO, CS, NR ⁵ , C (R ⁶ ) ₂ , CR ⁶ = CR ⁶ , C = C, CH = N, phenylene, naphthylene, pyridylene, cycloalkylene or cycloalkenylene, each having 3 to R 7 is hydrogen, benzyl, phenyl, fluorine, chlorine, alkyl of 1 to 4 carbon atoms, hydroxy, trifluoromethyl , Cyano, carboxy, amino, alkylamino each having 1 to 4 carbon atoms in the alkyl radical or carbalkoxy having 1 to 4 carbon atoms in the alkoxy radical.

Of very particular interest are compounds of the general formula (I) in which

R and R 'are identical or different and are each a phenyl radical or a thienyl, furyl or pyridyl radical, where the phenyl radical optionally one or two identical or different substituents from the group nitro, cyano, acido, halogen, trifluoromethyl, hydroxy , Amino, alkyl, alkoxy, alkylamino or alkylmercapto each having 1 or 2 carbon atoms in the alkyl groups.

1 and R 'are each the same or different and each represent a straight-chain or branched hydrocarbon radical having up to 6 carbon atoms, which is optionally interrupted by an oxygen in the chain and which is optionally substituted by fluorine, chlorine, hydroxyl, Phenyl or phenoxy.

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2 2 '4 4' "

R, R, R and R are the same or different and each represents hydrogen, straight-chain or branched alkyl radical having up to 4 carbon atoms, which is optionally substituted by fluorine, chlorine, hydroxyl, phenyl or amino. ,

3 3 '

R and R are the same or different and each represents hydrogen, alkyl having 1 to 4 carbon atoms, phenyl, benzyl or phenethyl, optionally substituted by hydroxy, fluorine or chlorine,

y and Y 'are the same or different and each have the meaning -COO-, -CONH-, -CO- or -SO ₃ -, and

X represents a bridge member having at least one non-ring-bonded CH ₉ group and at most 9 adjacent CH, groups as chain members, wherein the bridge member additionally in any order 1 to 3 identical or different chain members from the group, 0, S, CO , CS, NR ⁵ , C (R ⁶ ) ₂ . CH = N, phenylene, naphthylene, pyrrylidene, cycloalkylene of 5 to 7 carbon atoms, piperazinylene, piperidylene, pyrrolydinylene or morpholinylene, wherein R ^{3 is} hydrogen, benzyl or alkyl of 1 to 4 carbon atoms and R is hydrogen, benzyl, phenyl , Fluorine, chlorine, alkyl of 1 to 4 carbon atoms, hydroxy, trifluoromethyl, cyano, carboxy or amino.

The compounds of the general formula (I) according to the invention have valuable pharmacological properties. Because of its circulation-influencing

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• Γι

i 1

- 12 -

They can be used as antihypertensive agents, as vasodilators, as cerebral therapeutics and as coronary therapeutic agents. Particularly noteworthy is their long-lasting effect, which reduces the frequency of application in the treatment of circulatory diseases. They represent an enrichment of pharmacy.

Depending on the nature of the starting materials used, the synthesis of the compounds of general formula (I) according to the invention by the individual process variants can be represented by the following formula scheme:

Process variant A

CH ₃ OOC

CH ₃ OOC .CH

CF

COO- (CH ₂ -CH ₂ -O) -H

CH.

-H ₂ O

HOOC

COOC ₂ H ₅

COOC ₃ H ₅

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2 34 71-

Process variant B

2-χ

COOH + HO- (CH ₂ ) g -OH

-2K ₀ O

COO (CH

2'8

COOC ₂ H

Process variant C

HN ¹

Ethanol -H ₂ O

H ₅ C ₂ OOC

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AP C 07 D / 234 718/0. - 14 - 59 702/11

The 1,4-dihydropyridine hydroxy derivatives of the formula (II) used as starting materials and the dihydropyridine-3-carboxylic acid derivatives of the formula (III) are known or can be prepared by known methods (cf DE-OS 2 117 571)>

The l> 4 ~ Dihydropyridincarbonsauren - the general formula (IV) are known or can be prepared by known methods (see, EP-OS 11 706),

The bifunctional compounds of general formula (V) are also known or * can be prepared by known methods (see * Beilstein Band ± _p 464-502).

The yliden-S-keto esters of the general formula (VI) are known or can be prepared by processes known from the literature (cf G, C Jones, The Knoevenagel Condensation in Org * Reactions Vd, XV, 204 ff * (1967) )

The enaminocarboxylic acid esters of the general formula (VII) used as starting materials are known or can likewise be prepared by methods known from the literature (cf., A, 'C _# Cope, 0 * Am »Chern * Soc, 67, 1017 (1945)) *

Suitable diluents for use in process variants A and B are all aprotic organic solvents "These preferably include ethers, such as dioxane, diethyl ether, tetrahydrofuran, glycol dimethyl ether or hydrocarbons, such as benzene ¹ ,

2 3 4 718 O

_ ι 5 -

Toluene, xylene or dimethylformamide, dimethylsulfoxide, acetonitrile, pyridine or hexamethylphosphoric acid diamide.

In the case of process variant C, it is also possible to use alcohols, e.g. Methanol, ethanol or isopropanol before 5 Partly used.

As water-binding agents (process variants A and C), all reagents customary for this purpose can be used, in particular the use of dicyclohexylcarbodiimide and the addition of a catalyst, such as, for example, "IQ 4-dimethylaminopyridine, is very advantageous.

The reaction temperatures can be varied within a wide range. In general, the reaction is carried out between 0 and 180 ^° C., preferably between 20 and 120 ^° C.

The reactions can be carried out at atmospheric pressure or at elevated pressure. In general, one works at atmospheric pressure.

The compounds of general formula (I) show interesting biological effects. They have a broad and versatile spectrum of pharmacological activity and are characterized in particular by their long-lasting effect. "In detail, the following main effects are mentioned:

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1. The compounds cause parenteral, oral and perlingual addition a significant and long-lasting enlargement of the coronary vessels. This effect on the coronary vessels is enhanced by a simultaneous nitrite-like heart-stressing effect.

They influence or change the heart metabolism in the sense of saving energy.

2. The excitability of the stimulus-forming and excitation-conduction system within the heart is reduced, resulting in an anti-flicker effect detectable in therapeutic doses.

3.. The tone of the smooth muscle of the vessels becomes

greatly reduced under the effect of the compounds. This vascular spasmolytic effect may occur throughout the vasculature, or manifest more or less isolated in circumscribed vascular regions (such as the central nervous system).

4. The compounds lower the blood pressure from normotas ^and <3. hypertensive animals and thus can be used as antihypertensive agents.

• 5th The compounds have strong muscular-spasmolvtische effects, these on - the smooth muscle of the stomach, intestinal tract, the genitourinary tract and the respiratory system become clear.

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The new active compounds can be converted in a known manner into the customary formulations, such as tablets, capsules, dragees, pills, granules, aerosols, syrups, emulsions, suspensions and solutions, using inert, non-toxic, pharmaceutically suitable excipients or Solvent. Here, the therapeutically active compound should be present in each case in 'a concentration of about 0.5 to 90 wt .-%' of the total mixture, i. in amounts sufficient to achieve the stated dosage margin.

The formulations are prepared, for example, by stretching the active compounds with solvents and / or carriers, if appropriate using emulsifiers and / or dispersants, e.g. in the case of using water as the diluent, organic solvents may optionally be used as auxiliary solvents.

Examples of adjuvants are:

Water, non-toxic organic solvents such as paraffins (eg petroleum fractions), vegetable oils (eg peanut / sesame oil), alcohols (eg ethyl alcohol, glycerine), glycols (eg propylene glycol, polyethylene glycol), solid carriers such as ground natural minerals (eg Kaolins, clays, talc, chalk), ground synthetic minerals (eg fumed silica, silicates), sugars (eg, raw, milk and dextrose), ₄ emulsifiers (eg polyoxyethylene fatty acid esters,

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Polyoxyethylene fatty alcohol ethers, alkyl sulfonates and aryl sulfonates), dispersants (e.g., lignin, spent liquors, methyl cellulose, starch and polyvinyl pyrrolidone) and lubricants (e.g., magnesium stearate, talc, stearic acid and sodium lauryl sulfate). -

The application is carried out in a customary manner, preferably orally or parenterally, in particular perlingually or intravenously. In the case of oral administration, tablets, of course, besides the said carriers, may also contain additives, such as sodium citrate. Calcium carbonate and dicalcium phosphate together with various adjuvants such as starch, preferably potato starch, gelatin and the like. Further, lubricants such as magnesium stearate, sodium lauryl sulfate and talc may be used for tableting. In the case of aqueous suspensions and / or elixirs intended for oral use, the active ingredients other than the abovementioned excipients may be mixed with various flavor enhancers or colorants.

In the case of parenteral administration, solutions of the active ingredients may be employed using suitable liquid carrier materials.

In general, it has been found to be beneficial to administer amounts of about 0.01 to 10 mg / kg, preferably about 0.05 to 5 mg / kg of body weight per day for effective results when administered intravenously, and for oral administration the

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4,5.1982.

AP C 07 D / 234 718/0 - 19 - 59 702/11

Dosage of about 0.05 to 20 mg / kg, preferably 0/5 to 5 mg / kg of body weight per day,

Nevertheless, it may be necessary to deviate from the stated amounts, * depending on the body weight of the test animal or the type of application route, but also on the basis of the species and their individual behavior towards the drug or their A'rt of. its formulation and the time or interval of administration. Thus, in some cases it may be sufficient to make do with less than the minimum amount mentioned above, while in other cases the above upper limit must be exceeded. In the case of the application of larger quantities, it may be advisable to divide these into several single doses-over the day. For the application in human medicine, the "same dispensing range is provided.

  S e ttin g isp ile

The invention will be explained in more detail below with reference to some examples.

Example 1 .

, [J. , 6-Dimethyl-5-ethoxycarbonyl-4- (3-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid 7 - /. "2,6-dimethyl-5-methoxycarbonyl-4--2-chlorophenyl) -1,4 -dihydropyridin-3-carbonsaure7 ~ 1,4-butandiylester

H ₅ C ₂ OOC

O.

COO- (CH ₂ ) ₄ OOC

CH.

3 H

'3 H

Process variant A

25 mmol of ethyl 2,6-dimethyl-5- (4-hydroxybutoxy) carbonyl-4- (3-nitrophenyl) -1,4-dihydropyridine-3-carboxylate are added together with 25 mmol of dicyclohexylcarbodiimide and 25 mmol of 2,6-dimethyl 5-methoxycarbonyl-4- (2-chlorophenyl) 1,4-dihydropyridine-3-carboxylic acid dissolved in 50 ml of anhydrous dimethylformamide and heated with the addition of 0.2 g of 4-dimethylaminopyridine for 4 hours at 100 ⁰ C- is then filtered off with suction, the filtrate diluted with methylene chloride and shaken out in each case with aqueous NaOH and HCl, dried and concentrated by rotary evaporation.

It is then chromatographed on silica gel with ether chromatographic

initialed.

Yield: 2.5%, amorphous foam.

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234718 O

H NM R:

¹ t .2 (t, 3H), 1.4-1.8 (m, 4H), 2.4 (s / i2H),

3.6 (s, 3H), 3.9-4.4 (m, 6H), 5.2 (s, 1H),

5.4 (s, 1H), 5.8 (s, NH), 5.3 (S ₇ NH), 6.9-

8.3 (m, 8H).

Example 2

Bis £ 2, 6-dimethyl-5-methqxycarbonyl ⁱ -4- (3-nitrophenyll-1,4-dihydropyridine-3-carbonsäure7-T, 6-hexandiy! Ester

H ₅ C ₂ OOC

NO.

COO- (CH _n ), -OCO

COOC ₂ H, -

3 H

Process variant B

50 mmol of 2,6-dimethyl-5-methoxycarbonyl-4- (3-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid are dissolved together with 50 mmol Dicyclohexvlcarbodiimid and 25 mmol of 1,6-hexanediol in 50 ml of anhydrous dimethylformamide and with the addition of 0.2 g of 4-dimethylaminopyridine for 4 hours at 100 ⁰ C stirred. The mixture is then filtered off with suction, the filtrate is diluted with methylene chloride and shaken out in each case with aqueous NaOH and HCl, dried in a rotary evaporator and recrystallized from methanol

 Melting point: 177-179 ° C, yield: 37%.

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Example 3

Bis-2,6-dimethyl-5-methoxycarbonyl-4- (2-chlorophenyl) -1,4-dihydropyridine-3-carboxylic acid J7-1,3-propanediyl ester

CH ₃ OOC

COO- (CH ₂ ) 3-OOC

'3 H ^CH 3 5 Process variant C

CH.

25 mmol of bis (3-aminocrotonic acid) -1,3-propandiylester are boiled together with 50 mmol of 2-Chlorbenzylidenacetessigsäuremethylester in 100 ml of absolute ethanol for 14 hours under N_ at reflux.

After cooling, the solvent is distilled off in vacuo and taken up with 50% aqueous ethanol. The semi-solid residue was recrystallized from methanol

Melting point: 200 to 203 ⁰ C; Yield: 50%.

1 5 Example 4

Bis-ZJ 2, 6-dimethyl-5-methoxycarbonyl-4- (3-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid triethylene glycol diester

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H ₅ C ₂ OOC

COO- (CH ₂ -CH ₂ -O) ₃ -

COOC ₂ H ₅

100 mmol 2, ö-dimethyl-S-ethoxycarbonyl ^ - (3-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid are reacted and worked up analogously to Example 2 with 50 mmol of triethylene glycol. Melting point: 113 to 120 ^° C; Yield: 32%.

Example 5

To-/! , O-Dimethyl-S-ethoxycarbonyl-4- (3-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid 1'-1-O-decanedioate

H ₅ C ₂ OOC

COO (CH

2 '10

COOC ₂ H ₅

100 mmol of 2,6-dimethyl-5-ethoxycarbonyl-4- (3-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid are reacted with 50 mmol of 1,10-decanediol analogously to Example 2

Melting point: 121 to 125 ^° C; Yield: 35%.

Example 6

BLs-2, 6-dimethyl-5-ethoxycarbonyl-4- (3-nitrophenyl-1,4-dihydropyridine-3-carboxylic acid, 7-1, 8-octanediyl ester

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71

COO- (CH ₂ ) Q-

COOC ₂ H ₅

100 mmol of 2, ö-dimethyl-S-ethoxycarbonyl ^ - (3-nitrophenyl) 1,4-dihydropyridine-3-carboxylic acid are reacted with 50 mmol of 1,8-. Octanediol analogously to Example 2 implemented. Melting point: 170 to 184 ⁰ C; Yield: 47%.

Example 7

Bis - /] 2/6-dimethyl-5-ethoxycarbonyl-4- (3-nitrophenyl-1,4-dihydropyridine-3-carboxylic acid, 7-1, 5-pentanediyl ester

H ₅ C ₂ OOC

COO- (CH ₂ ) ₅ -O ₂ C

CH,

COOC ₂ H ₅

3 H

3 H

100 mmol of 2,6-dimethyl-5-ethoxycarbonyl-4- (3-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid are mixed with 50 mmol of 1,5-pentanediol. implemented analogously to Example 2. Melting point: 145 ^° C; Yield: 11%.

Example 8

5 bis-2,6-dimethyl-5-ethoxycarbonyl-4- (3-nitrophenyl) -

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-.25 -

1,4-dihydropyridine-3-carbonsäure7 ~ 1,4-bis- (2-hydroxyethoxy) -benzene-diesters

COO- (CH ₂ ) ₂ - <

2 '2

-0OC

CCOC ₂ H

3 H

100 mmol of 2, G-dimethyl-S-ethoxycarbonyl - ^ - (3-nitrophenyl) -1, 4-dihydropyridine-3-carboxylic acid are reacted with 50 mmol of 1,4-bis (2-hydroxyethoxy) benzene analogously to Example 2

Melting point: 160 to 190 ⁰ C (dec.); Yield: 49%.

Example 9

Bis-2,6-dimethyl-5-ethoxycarbonyl-4- (3-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid C ' ⁷ tetraethylene glycol ·

diesters

N0 "

COO- (CH ₂ -CH ₂ -O) ₄ -O C

COOC ₂ H ₅

100 mmol of 2,6-dimethyl-5-ethoxycarbonyl-4- (3-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid are reacted and worked up analogously to Example 2 with 50 mmol of tetraethylene glycol. ^: Melting point: 93 - S8 ° C Yield: 16%.

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Example 10

Bis - [2 , 6-dimethyl-S-isopropoxycarbonyl-1- (3-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid 7 ~ 1,6-hexanediyl ester

COO

3 H

CH N CH H

25 mmol of bis (3-aminocrotonic acid) -1,6-hexanediyl ester are reacted analogously to Example 3 with 50 mmol of 3-nitrobenzylidene acetoacetate diisopropyl ester. Melting point 120-136 ⁰ C Yield: 83%.

Example 11

Bis - / [2 _/ 6-dimethyl-5-methoxycarbonyl-4- (2-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid 7 ~ 1,6-hexanediol ester

CH ₃ OOC

COO- (CH ₀ ) - OOC

CH.

CH.

Le A 20 638

25 mmol of bis (3-aminocrotonic acid) -1,6-hexanediyl ester are reacted with 50 mmol of methyl 2-nitrobenzylideneacacetate analogously to Example 3. Melting point 88-95 ° C Yield 82%.

Example 12

Bis - / - 2, 6-dimethyl-5-methoxycarbonyl-4- (2-chlorophenyl) 1,4-dihydropyridine-3-carboxylic acid 7-hexanediyl ester

CH OO

OOCH,

CH

25 mmol of bis (3-aminocrotonsäure) -1,6-hexandiylester be reacted with 50 mmol of 2-Chlorbenzylidenacetessigsäuremethylester analogously to Example 3. Melting point: 152-158 ⁰ C Yield 27%.

Example 13

Bis-2,6-dimethyl-5-ethoxycarbonyl-4- (3-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid 7-N, N'-bis (2-hydroxyethyl) piperazine diester

Le A 20 638

H ₅ C ₂ OOC

-CH ₂ -CH ₂ -OO

100 mmol of 2, ö-dimethyl-S-ethoxycarbonyl ^ - (3-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid are analogous to Example 2 with 50 mmol of N, N'-bis (2-hydroxyethyl) piperazine implemented. Melting point: 20 3 - 208 ⁰ C Yield: 18%.

Example 14

Bis -Q., S-dimethyl-S-ethoxycarbonyl-3- (3-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid J7-bis-hydroxyethylisulfide diester

H ₅ C ₂ OOC

, NO,

COO-CH ₂ -CH ₂ -S-Ch ₂ -CH ₂ -OOC

NO,

OOC, Η

100 mmol of 2, δ-dimethyl-S-ethoxycarbonylM- (2-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid are reacted analogously to Example 2 with 50 mmol of bis-hydroxyethyl sulfide

 Yield 70%.

Le A 20 638

Example 15

Bis -., / "2, ö-dimethyl-S-ethoxycarbonyl ^ i- (3-nitrophenyl) 1 ^ -dihydropyridin-S-carbonsäureJ'-i, 6-hexanediyl

H ₅ C ₂ OOC

COOC_H "

2 D

H.

25 mmol of bis (3-aminocrotonic acid) -1,6-hexanediyl ester are reacted analogously to Example 3 with 50 mmol · 2-Trifluoromethylbenzylidenacetessigsäureethylester. Melting point: 129-139 ⁰ C Yield 4 9%.

Example 16

Bis- / 7,6-dimethyl-5- (2-methoxy) -ethoxycarbonyl-4- (3-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid Il7-1 / 6-hexanediyl ester

CH.

OCC

CCCH ₂ -CH ₂ -O-CH ₃

Le A -20 638

25 mmol of bis (3-aminocrotonic acid) -1, β-hexanediyl ester are reacted analogously to Example 3 with 50 mmol of 3-nitrobenzylideneacetic acid 2-methoxyethyl ester. Melting point 144-156 ⁰ C. Yield 50%.

Example 17

'Bis- ( 2,6-dimethyl-4-carbonyl-4- (2-chloro-5-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid, β-hexanediyl ester

- (CH

₂ ) ₆

25mmo! Bis (3-aminocrotonic acid) -1, β-hexanediyl esters are reacted analogously to Example 3 with 50 mmol of 2-chloro-5-nitrobenzylidene-2,4-butanedione. Melting point 147-153 ⁰ C Yield 46%.

Example 18

5 BIs - /! 2, 6-dimethyl-5-ethoxycarbonyl-4- (3-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid I7-E-1,4-bis (hydroxymethyl) cyclohexane diester

Le A 20 638

H ₅ C ₂ OOC

trans

CH ₂ -OOC

COOC ₂ H ₅

50 mmol of 2,6-dimethyl-5-ethoxycarbonyl-4- (3-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid are reacted analogously to Example 2 with 25 mmol of Ξ-1,4-bis (hydroxymethl) cyclohexane.

Melting point 172-188 ° C Yield 15%.

Example 19

Bis - /, 2, 6-dimethyl-5-ethoxycarbonyl-4- (3-nitrophenyl) 1, 4-dihydropyridine-3-carbonsäure7-1, 4-bis- (hydroxyrnethyl) -benzoldiester

H ₅ C ₂ OOC

00-CH.

CH ₂ -O-C

0OC ₂ H ₅

CH "N ' ^CH 3

50 mmol · 2, β-dimethyl-5-ethoxycarbonyl-4- (3-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid are prepared as an Example Example 2 with 25 mmol · 1,4-bis- (hydroxymethyl ·) benzene · implemented. Melting point: 244-59 ° C. Yield: 30%.

Le A 2 0 6 38

3471

Example 20

Bis-2,6-di-ethyl-5-ethoxycarbonyl-4- (2-cyanophenyl) 1,4-dihydropyridine-3-carboxylic acid 7,1,6-hexanediyl ester

H ₅ C ₂ OOC

OO- (CH ") _C -OOC 2. o

H-

25 mmol of bis (3-aminocrotonic acid) -1, 6-hexadinylester are reacted with 50 mmol of ethyl 2-cyanobenzylideneacetate analogously to Example 3. Yield: 8 0% '.

Le A 20 638

Example 21

Bis-, δ-dimethyl-S-ethoxycarbonyl-ii- (3-nitrophenyl) -1,4 · dihydropyridine-3-carboxylic acid] -1,6-hexanediylamide

H ₅ C ₂ OOC

CH-

NO-

CO-NH- (CH ₂ ) ₆ -NH-OC

CH;

NO;

N H

CH ₃

25 mmol of 2,6-dimethyl-5-ethoxycarbonyl-4- (3-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid are reacted analogously to Example 2 with 12.5 mmol of 1,6-diaminohexane.

Yield: 27% (mp .: 147-152 ⁰ C).

Example 22

Bis [2,6-dimethyl-5-methoxycarbonyl-4- (2-chlorophenyl) -1,4'-dihydropyridine-3-carboxylic acid] -1,8-octanediyl ester

CH ₃ OOC

CH ₃ Le A 20 6 38

Cl

COO- (CH ₂ ) a -OOC

CH:

Cl COOCH ₃

CH ₃ JJ CH ₃

25 mmol of bis (3-aminocrotonic acid) -1,6-hexanediyl ester are reacted with 50 mmol of 2-Chlorbenzylidenacetessigsäuremethylester analogously to Example 3.

Yield 80% amorphous substance.

¹ H-NMR (CDCl ₃ ): ei = 1.0-1.4 (m, 8H), 1.4-1.7 (m, 4H), 2.2 {2 $,

12H), 3.6 (s, 6H), 4.0 (t, 4H), 5.4 (s, 2H), 5.9 (s, NH), 6.9-7.5 (m, 8H) '.

Example 23

Bis [2,6-dimethyl-5-ethoxycarbonyl-4- (3-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid] -N, N'-bishydroxyethylharnstoff diesters

H ₅ C ₂ OOC

.. NO

COO- (CH ₂ ) ₂ -NH-C-NH- (CH ₂ ) ₂ ~ 00C

CH ₃ N CH ₃ H

CH,

NO-

COOC ₂ H ₅

N CH ₃ H

Preparation analogous to Example 2 from N, N'-Bishydroxyethylharnstoff and 2,6-dimethyl-5-ethoxycarbonyl-4- (3-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid.

Yield: 32%, m.p .: 178-187 ° C. Le A 20 6 38

Example 24 -. '

Bis- [2,6-dimethyl-5-methoxycarbonyl-4- (2-nitrophenyl) -1,4-dihydropyridine-3 "-carboxylic acid] bis (2-hydroxyethyl) sulfide diester

-CH ₃ OOC

CH,

NO-

COO- (CH ₂ ) ₂ -S- (CH

CH,

CQX

2 I 2

N H

NO ₂ COOCH ₃

CH,

Preparation analogous to Example 3 of bis (3-aminocrototonic acid) bis (2-hydroxyethyl) sulfide diester and methyl 2-nitrobenzylidenacetessigsäuremethylester.

Yield: 80% amorphous substance

¹ H-NMR _(CDCl3): J ~ = 2.3 (2s, 12H) '2.4-2.8 (m, 4H), 3.6 (s, 6H),

3.9-4.3 (m, 4H), 5.8. (s, 2H) -, 6.3 (s, NH), 7.1-7.8 (m, 8H). :

Le A 20 63 8

Example 2 5

Bis [2,6-dimethyl-5- (2-methoxy) -ethoxycarbonyl-4- (2-chlorophenyl) 1,4-dihydropyridine-3-carboxylic acid] -1,6-hexanediyl ester

CH ₃ O- (CH ₂ ) ₂ 00C

CH-

Cl

COO- (CH ₂ ) 6-OOC

CH-

CH,

Cl

COO- (CH ₂ ) ₂ -OCH,

CH,

Preparation analogous to Example 3 from 25 mmol of bis (3-aminocrotonic acid) 1/6-hexanediyl ester and 50 mmol of 2-chlorobenzylideneacetic acid 2-rnethoxyethylester.

«Yield: 67% (mp .: 135-143 ° C).

Example '26

Bis [2,6-dimethyl-5-ethoxycarbonyl-4- (2-trifluoromethylphenyl) -1,4-dihydropyridine ~ 3-carboxylic acid] -bis- (2-hydroxyethyl) -SU ^- If id diesters

H ₅ C ₂ OOC

CH,

CF,

COO- (CH ₂ ) ₂ -S (CH ₂ ) ₂ -OOC

Le A 20 6-38

Preparation analogous to Example 3 from 25 mmol of 'bis (3-aminocrotonsäure) bis (2-hydroxyethyl) sulfide id -.ter.ter and 2-Trif luormethylbenzylidenacetessigsäureethylester.

Yield: 79%. amorphous substance.

¹ H-NMR (CDCl ₃ ) : cT = 1.2 (t, 6H), 2.2 (s, 12H), 2.4-2.8 (m, 4H),

3.9-4.5 (m, 8H), 5.6 (s, 2H) ,, 6.7 (s, NH), "* 7.1-7.7 (m, 8H).

Example 27 »

Bis- [2,6-dimethyl-5-ethoxycarbonyl-4- (3-nitrophenyl> -1,4-dihydro-.0-pyridine-3-carboxylic acid] bis (2-hydroxyethyl) disulfide diester

H ₅ C ₂ OOC

NO-

COO- (CH ₂ ) ₂ -SS- (CH ₂ ) ₂ -OOC

CH ₃ CH ₃ .H

NO,.

COOC ₂ H ₅

CH,

12.5 mmol of bis (2-hydroxyethyl) disulphide were reacted analogously to Example 2 with 25 mmol of 2,6-dimethyl-5-ethoxycarbonyl-4- (3-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid. -

Yield: 77% amorphous substance.

¹ H-NMR (CDCl ₃ ) :

.2 (t, 6H), 2.4 (s, 12H), 2.7-3.1 (m, 4H), 3.9-4.5 (m, 8H), 5.1 (s, 2H), 6.4 (s, NH), 7.2 8.2 " (m, 8H) -

Le A 20 638

2 3 4 718 O

Example 28

- 30 -

Bis- [2,6-dimethyl-5- {2-methoxyethoxycarbonyl) -4- (3-nitrophenyl) -1,4-dihydro-pyridine-3-carboxylic acid] -1,8-octanediyl ester

NO-

CH ₃ O- (CH ₂ ) ₂ -OOC

CH

COO- (CH ₂ ) ₈ -OOC

N H

CH,

CH ₃

NO,

COO- (CH ₂ T ₂ -OCH-

CH ₃

25 mmol of bis (3-aminocrotonic acid) -1,8-octandiylester are reacted analogously to Example 3 together with 50 mmol of 3-nitrobenzylideneacetic acid 2-methoxyethyl ester.

Yield: 75% (mp. 146-15O ° C).

Example 29

Bis [2,6-dimethyl-5- (2-methoxyethoxycarbonyl) -4- (3-nitrophenyl) -1,4-dihydropyridine-3-carboxylic acid] -1,4-bis (hydroxymethyl) benzene diester

NO-

CH ₃ O- (CH ₂₎ 2-OOC

CH:

COO-CH

CH ₂ -

CH ₃

NO-

COO- (CH ₂ ) ₂ -OCH ₃

CH,

Le A 20 638

• 23471 80

Preparation analogous to Example 3 from 25 mmol of bis (3-aminosrdtonsäure) -1,4-bis (hydroxymethyl) benzene diester and 50 mmol of 3-nitrobenzylidene acetoacetic acid 2-methoxyethyl ester ^

Yield: 67% (mp. 159-162 ° C).

5 Example 30

Bis- [2,6-dimethy1-5- (2-methoxyethoxycarbonyl) -4-β-trifluoromethylphenyl) -1,4-dihydropyridine-3-carboxylic acid] -bis- (2-hydroxyethyl) sulfide diesters

CH ₃ O- (CH ₂ ) ₂ -OOC

CH,

Col

N H

CF ₃

COO- (CH ₂ ) ₂ -S- (CH ₂ ) ₂ -OOC

CH,

CH ₃

COO- (CH ₂ ), -OCH

Preparation as in Example 3. Yield: 28% (mp .: 100-112 ° C).

Le A 20 638

"B ice piel 31.

BiS - [2,6-dimethyl-5-methoxycarbonyl-4- (1-naphthyl) -1,4-dihydro-pyridine-3-carboxylic acid] -1,8-octanediyl ester

CH ₃ OOC

CH ₃

oils

COO- (CH ₂ ) g-OOC

N H

CH:

COOCH,

Representation analogous to Example 3

 Yield: 76% amorphous substance. - ...

¹ H-NMR _(CDCl3): ci ^ O.8-1.5 (m, 12H) / 2.3 (2s, 12H), 3.5 (s, 6H),

3.6-4.1 (m, 4H), 5.8 (s, 2H), 6.1 (s, NH), 7.1- "'7.8 (m, 14H)."

Le A 20 638

Claims (3)

R and R 1 are the same or different and each represents an aryl radical or a thienyl, furyi, - pyrryl, pyrazolyl, xraidazolyl, oxazolyl, isoxazolyl, thiazolyl, pyridyl ,. Pyridazinyl, pyrimidyl ,,. Pyrazinyl, naphthyl, quinolyl ', jsochinolyl, indolyl, benzimidazolyl, quinazolyl or quinoxalyl radical, where the aryl radical and also the heterocycles optionally have 1 to 3 identical or different substituents from the group consisting of phenyl, alkyl, alkenyl, alkoxy, Alkenoxy, alkylene, dioxyalkylene; Halogen, monofluoroalkyl, polyfluoroalkyl monofluoroalkoxy, polyfluoroalkoxy, hydroxy »amino, alkylamino, nitro, cyano, azido, carboxy, carbalkoxy, carbonamido, sulfonamido or SO« alkyl (m = O to 2), 11 R and R,! are the same or different and each represents a straight-chain, branched, or cyclic, saturated or unsaturated hydrocarbon radical which is optionally interrupted by 1 or 2 oxygen atoms in the chain, and which is optionally substituted by halogen, hydroxy or by a phenyl -, phenoxy, phenylthio or phenylsulfonyl group, which in turn may be substituted by halogen, cyano, dialkylamino, alkoxy, alkyl, trifluoromethyl or nitro, 1 2 R ₄ R and R - have the above given condition, with enaminocarboxylic acid esters of the general formula (VII). - \ R ⁴ -C = CH-YCY * -CH = CR ⁴ ' (VII) ₁ R ³ NH HNR 3. ¹ in which 1 * 2 * 3 * 4 ' R *; R ^: VR '. "- ι, R ^J , R and Y" the above * -. Have meaning, where Y. ' not for one "* Carbonyl group stands ,. ' τ in equivalent amounts with elimination of water at Temperatures between ^{0 0} C and 180 ⁰ C converts, or   B) 1,4-dihydropyridinecarboxylic acids of the general formula (IV) R ¹ OOC I COGH in which ' . - R, R, R j R and R have the abovementioned meaning, " in the presence of an inert organic solvent and optionally in the presence of a condensing agent with a bifunctional compound of the general formula (V) in which X has the abovementioned meaning and Z and Z * are identical or different and represent hydroxyl, mercapto or the radical NR H, wherein R has the meaning indicated above. 05/04/1932 AP C 07 D / 234 718/0 59 702/11 in a molar ratio of about 2; 1 at temperatures between OC and 180 ⁰ C umsetztV obtain only compounds of general formula (I) according to this variant / in which Y and Y ' do not stand for a carbonyl group, odgr C) Yliden-β-ketoesters of the general formula (VI) R-CH = C COR- ² COOR " (VI) in which 1 to 5 identical or different chain members from the group 0, S, SO, SO ₂ , CO, CS, NR ⁵ , C (R ⁶ ) ₂ , CR ⁶ = CR ⁶ , C = C, CH = N, arylene, heteroarylene, cycloalkylene, cycloalkenylene, piperazinylene, piperidylene, Pyrrolidinylen or .Morpholinylen may contain, wherein R is hydrogen, alkyl or aralkyl •, and R is hydrogen, aralkyl, aryl, heteroaryl aryl, alkyl, alkenyl, alkynyl, alkoxy, "alkenoxy, alkynoxy, alkylene, dioxyalkylene, Halogen, Monof luoralkyl ', Polyf luoralkyl, Monofluoralkoxy, Polyfluoralkoxy, hydroxy,. Amino, alkylamino, nitro, cyano ¹ , azido, carboxy, carbalkoxy, carbonamido, sulfone ·. amido or SO-alkyl (m = 0 to 2) and in which, in turn, the aryl, alkyl and heteroaryl radicals may be substituted by one to three of the same Le A 20 638 4 _# 5,1982 AP C 07 D / 234 718/0 59 702/11 various radicals from the group aryl, alkyl · ,. Alkoxy, aralkyl, dioxyalkylene, halogen, monofluoroalkyl, polyfluoroalkyl, monofluoroalkoxy, polyfluoroalkoxy; Hydroxy, amino, alkylamino, nitro, cyano, acido, carboxy, carbalkoxy, carbonamido, sulfonamido or-SO-alkyl (m '= 0 to 2). and their pharmacologically acceptable acid addition salts, characterized in that A) 1,4-4 Dihydropyridinhydroxyderivate ^he formula (II) , R · Ps-OOC Y-X-OH (U) ₁ in which R, R ¹ , R, R ³ _f R, Y and X have the abovementioned meaning, in an inert organic solvent in the presence of water-binding agents with "dihydropyridine-3-carboxylic acid derivatives of the general formula (III) COOR (Ill), 4.5.1982 AP C 07 D / 234 718/0 - 45 ~ 59 7.02 / 11 in which 2 '4 4' . ^ .- • v. 10 R, R, R and R are the same or different and - ^ 'in each case for hydrogen, a straight-chain or branched, cyclic, saturated or unsaturated hydrocarbon radical, optionally substituted -15 'is halogen, hydroxy, aryl or amino or an amino group, which in turn may optionally be substituted by a carbon radical, - wherein this hydrocarbon radical straight-chain, branched, cyclic, saturated or may be unsaturated and in turn optionally substituted, 3 ' R "and R are the same or different and each ν J is hydrogen or an optionally substituted straight chain or ver branched alkyl radical which is optionally interrupted by one or two oxygen atoms in the alkyl chain or represents an optionally substituted aryl or aralkyl radical, Le A 20 638 Y and Y 'are the same or different and each has the meaning 0 0 " 0 0 '". -CO-, -C-NH-, -CS-, -C- or -SO ₃ -   have and . ' > X for a bridge link with at least one CHp group and at most 9 adjacent 'CHp groups, this bridge   additionally in any order 3 "^ * 4 4 *
R _f R * "· -, R ' _f R / Y and Y' are those given above Have meaning in the presence of inert organic solvents in molar ratios * 'of about 2: 1 at temperatures between 0 and 180 ⁰ C. * Method according to item I ₄ characterized characterized,. that the reaction is carried out at temperatures between 20 ⁰ C and 120 ⁰ C »