DE1929921A1 - New 1-alyl-1,2,5,6-tetrahydro-3-pyridylmethyl-carboxylic acid esters and their acid addition salts and quaternary ammonium compounds - Google Patents

Description

Case 1/321
We / ER

Dr. F Zumetein »en. - Dr. E. A · ⁹ ·? Dr.lt Koenlg.berger - Dip «. Phy ·· »· Woodcutter

Dr. F. Zumstain | un.

Patent attorney "

8 monks 2. BräuhouMtraße 4 / IU

. C. p. BOEHRINGER SOHIi, Ingelheim / Hh

New 1-alkyl-1,2,5, δ-tetrahydro ^ -pyridylmethyl-carboxylic acid esters as well as their acid addition salts and quaternary ammonium compounds

The invention relates to new 1-alkyl-1,2,5,6-tetrahydro ~ 3 · pyridylmethyl carboxylic acid esters of the general formula

1 A

CH ₉ -OCC- IU

^R 4 '

UJ

909881/1709

2 -

as well as their acid addition salts and quaternary ammonium compounds.

In this formula mean;

R-, one optionally through a cyano or alkoxy group substituted alkyl radical with 2-10 carbon atoms, a branched alkyl radical with 3-5 carbon atoms, an alkenyl radical optionally substituted by a halogen atom and having 2-3 carbon atoms, a

* Alkynyl radical with 2-3 carbon atoms, a cycloalkyl radical with 3-6 carbon atoms or a phenylalkyl radical,

Rg hydrogen, methyl, the hydroxyl group or a chlorine atom,

R, hydrogen, the phenyl or a cycloalkyl radical with 5-6 carbon atoms or R ₂ and R * together form a 5- or 6-membered cycloaliphatic ring and R /. a phenyl radical, where, if R _x and R each represent a phenyl ring, these rings are optionally connected to one another in the o-position to the point of attachment with the OC-C atom of acetic acid by a direct bond or via an oxygen atom.

I.

The new connections can be displayed

a) by esterification of a compound of the general formula

- X

^R l 909881/1709 _ ₃ "

1929S21

wherein R-. has the meaning given above and X denotes the hydroxyl group or a halogen atom with a compound of the general formula

^K 2 \ I!

R ₃ -GCY III

^S 4

wherein Rp ₅ R * and R, have the meaning given above and

Y is the hydroxy "or an alkoxy group or a metal means or _o other suitable for esterifying derivative of this compound by known traversing en ₉ as described for example in Houben-Weyl, Methoden der Organischen Chemie" Band XEE, page 508 ff (1952) are described
b) by alkylating an ester of the general formula

ί? A.

O - c - C - IU

LJ

^R 4

where Rp ₅ IU raaä R, have the meaning given above, on the nitrogen atom aes tetrahyropyridine rings according to known methods, such as, for example, in Houben-Weyl, Methoeaen (^ anisohen Glaemies Volume XI / 1

09881/1709

Page 3 ff (1957) are cited.

The end products of the general formula I thus obtained can then be converted into their acid addition salts by customary methods or the quaternary ammonium compounds are converted.

The esterification of a compound of the general formula II is preferably carried out using a customary esterifying agent, for example an acyl halide or anhydride or by reacting a compound of the formula II, in which X is a halogen atom, with a salt of a carboxylic acid of the general formula III; The reaction of an acid ester of the formula III (Y = O-alkyl) with a carbinol of the formula II (X = OH) has also proven particularly suitable.

The compounds of general formula II used as starting materials in process a) are also new; she can be prepared, for example, by alkylating a Z ^ jSie-Tetrahydropyridln - ^ - carboneäüreaikylesters am Nitrogen atom and subsequent reduction of the * ester at- * for example with iifiaiumaluminum hydride or by reduction of a quarinary pyridylcarbinol of the formula

^^^^ "* ^{w 0H}

I ₊ I Hal "

Marg

98 8 1/1 * öSr "- ^" ife '^ - ii-

wherein it-, has the meaning given above, by means of Sodium borohydride "

The alkylation of a compound of general formula IV may, after all conventional "ethcden atom of the substitution of a hydrogen, which is connected to a .Stickstoffatom ₅ carried out in a manner known per se werderfreak>"

3g you can, for example, a compound of formula I? with an alkyl halide in the usual manner into the one on the nitrogen atom Transfer substituted compound ,, Likewise arrived one to the new connections by solving a secondary amine of the general formula IV with an Aide = hyü in the presence of formic acid "

The 1 _S 2 ₉ 5 ₉ 6 ° Setrahydro = '3 ^c -pyridylmethylcarboxylic acid esters of the general formula IV are also new compounds; they can be obtained, for example, by transesterification dos l _p 2 ₉ 5 ₉ 6 ~ Ietrahydro "3-pyridylmethyl alcohol with an ester, preferably the methyl ester _{8 of} the desired acid of the general formula III (Y = OH)"

If desired, the end products of the general formula I can be converted into their acid addition salts or quaternary ammonium compounds . Acids that provide physiologically harmless salts, such as hydrohalic acids, can be used for this conversion.

- 6 -399931/1709

Sulfuric acid, phosphoric acid, nitric acid, oxalic acid, Citric acid, V / monic acid, puraaric acid, sharkic acid, acetic acid, Propionic acid, butyric acid, methanesulfonic acid, Bern stinic acid

The quaternary ammonium compounds can be prepared by reacting a compound of the form ::,.; -! "... with all compounds suitable for quaternization, for example nit'alkyl or aralkyl halide <ü octr cn !.; a dialkyl sulfate»

liach the method described above may include, _o 3 _O u.ie following compounds., preferably in i? becoming traktorra their Jäure "additioHSBSilze or qua ternary en Amcioniuicsalze prepared

1-ethyl-1 j 2, 5, ö-tetrahydro-S-pyridyliaethjl-bensilsäureester, 1-n-propyl-1,2,5 '6 ~ tetrahydro-3-pyridylmethyl ^e benzilsäureeeter, 1-isopropyl "· !, 2 , 5,6-tetrahydro-> 3-pyridylmettiylbenzilic acid ester, in-butyl-1,2,5-6-tetrahydro-3-pyridylmethylbenzilic acid ester, in-amyl
pyridylmethyl-benzilic acid ester, l-

dro-3-pyridylraethyl-benzilic acid ester, 1-n-hexyl-1,2,5,6-tetrahydro-3-pyriaylmethyl-benzilic acid ester, 1-n-heptyl, 2,56-tetrahydro-3-pyridylmethyl-benzilic acid1; he, 1-n- octyl-1,2,5, e-tetrahydro ^ -pyridylmethyl-benzilic acid ester, 1-n-nonyl-1,2,5 ₁ e-tetrahyaro. ^ - pyridylmethyl-benzilic acid ester, 1-n-deoyl- 1,2,5,6-tβtrahydro-3-pyridylmethyl-benzii-

- 7 -909181/1709

/ -V: SADOBJGINAL *

acid ester, l-ß- (cyanoethyl) -1,2,5,6-tetrahydro-3-pyridylmethyl-benzilic acid ester, l-ß- (methoxyethyl) -1, 2, 5,6-tetrahydro-3-pyridylmethyl-benzilic acid ester, 1-Cyclopropyl-1,2,5,6-tetrahydro ~ 3-pyridylmethyl-benzilic acid ester, 1-allyl-1,2,5,6-tetrahydro-3-pyridylmethyl-benzilic acid ester ', 1- (3-chloro-allyl) -1,2,5,6-tetrahydro-3-pyridylmethyl-benzilic acid ester, 1-propargyl-l, 2,5,6-tetrahydro-3-pyridylmethyl-benzilic acid ester, 1-phenylethyl-1,2,5,6-tetrahydro -3-pyridylmethyl-benzi-acid ester, 1-ethyl-1,2,5,6-tetrahydro-3-pyridy! Methyl- «-cyclopentyl- cc -phenylacetic acid ester, 1-ethyl-1,2,5,6- tetrahydro-3-pyridylmethyl-cyclohexyl-et-phenylacetic acid ester, 1-ethyl-1,2,5,6-tetrahydro-3-pyridylmethyl-1'-phenyl-cyclopentane-carboxylic acid ester, 1-ethyl-1,2,5,6 -tetrahydro-3-pyridylmethylhexahydro-bQEilic acid ester.

The new compounds of general formula I and their acid addition salts and quaternary ammonium compounds have strong pharmacological, especially spasmolytic and central sedating properties. Not only do they have the same potency as that known antispasmodic AfROPIN, but embody a new type of antispasmodic, as the side effects that have hitherto been regarded as indispensable for such substances, such as mydriasis, tachycardia and, in some cases, secretion inhibition. practically completely absent. Particularly noteworthy is the "extraordinarily cheap RelaMon, between the desired spasmolytic effect of the undesirable

90988 1 / 1.7Q9. , '. ......

ten mydriatic side effect.

Lacrimation and salivation remained in the animal experiments applied doses also unaffected. Neither there Tachycardia was observed, and with some of the new compounds also the secretion-inhibiting effect des ÄTROPINE is practically completely absent, are, in the case of the invention Connections almost eliminated all undesirable side effects of ATROPIN.

Those compounds of the general formula I have proven to be particularly effective in which R ^ is an alkyl group with 2 »6 carbon atoms. or the allyl group, R «denotes the hydroxyl group and FU and R ^ denote phenyl groups.

As a dose for the application of the new compounds of the general formula X are 0.1 to 50, preferably 1 to -5 mg / dose suggested.

The compounds according to the invention can be used alone or in Combination with other active ingredients according to the invention, possibly also in combination with other Phan »- Medicines such as hypnotics or tranquilizers are used. They can be used in all pharmaceutical preparation forms and can, for example, in Pills, tablets, coated tablets, ointments, suppositories »Lö-

■, ■■. ■■■■. "■. '■■■ - 9 -

90 98 81/1709

8AD QRiGWAL

solutions and injection solutions are incorporated «

The following examples serve to provide a more detailed explanation the invention?

Beispl_el_l

6- = tetrahydro- = 3-pyridylmethyl- = benzil-

g_g-ure.eg_t_er (according to method a) _

19> 7 g (IO O ₅ MoI) 1-n-hexyl-1,2,5,6-tetrabydro - 5-pyridylcarbinol and 26.6 g (0.11 mol) Benzilsäuremethylester who · = the sequentially at 80 C Dissolved in 100 ml of absolute n-heptane, after adding 1 nl of calcium diethylate solution (4 μg of Na in 100 ml of methanol), the mixture is refluxed for 2 hours and the methanol which has been separated off is collected in a water separator completion of the transesterification is filtered about 80 ⁰ O warms solution over active carbon and in Wass erstrahl vacuum concentrated <, yield of Bass 37 g 73% dc Th ο (au® Isopropyläthsr) ° rom mp ₀ = 57 -. 58 ⁰ Oo Hydrobroraid ( from alcohol)! Mp, ~ 135 O ₀ Methanesulfonst (from alcohol)? Pp. = 141 - 14 ?? ⁰ C BroEM & thjlmti Fp ₃ 205 - 206 ⁰ Go

is obtained as follows:

- 10 -

9098 81/1709

Mon

a) 22.5 g (0.1 KoI) 1-n-hexyl-i, 2., 5,6-tetrahydronicotinic acid methyl ester with a boiling point of 0.01 - 90 - 95 ° C- become a solution within one hour while stirring of 2.1 g (0 ₅ 055 mol) of LiAIu ₄ in 200 ml of absolute ether. After two hours of refluxing • it is cooled, carefully decomposed with 10 ml V / water and turbinated for an additional hour the residue is filtered several times with j sodas Ätlierpor functions nachgewseehen and DAS FII "burr at the end isL vacuum aai., 40 restricted ^u G aarupöse the residue is distilled in _a HoGhvaktimß Kaa erLält Ce.c 1-ii-l-Hesyl , 2, 5 »6" üetrah ^ ciro '»3-py:;. Idylt-earl) isiol a2 & ■■ ^ r ^ .lcr.ss oil ^ oia 7 - j: .. _c ^ 115 = - ■ 120 ° ί? _β in one form • ψοη 16 j 5 g - 84 ^ g. TIi ο

a) 1OS s 12 g ilHol) 3 ° -PYrj, ^ 'i2? «iÄ ^ c ^ rciaol ü-icl Π ρ .13 g. (1.05- Hol) n-Kexylbromid are dissolved in 400 najletbasol and 3 Sage is <? Αΐϊ $ Μ - §: <£ 3 £ ι1α & 3 $ ~ ύΘΏ Vessel on 6C ⁰ J GL-warms ₀ In the with 2. .. '· liter of methanol ^ eraüaSöe lösiiD.g be Rühren.innerhalb' of 50 minutes at 15 ⁰ C in portions 62 ₉ 4 g (I '65'Mol) XiaBH entered _o - Me reaction solution is stirred for 75 minutes and then, at a Badtemperatür of 60 ⁰ C in vacuo "the residue is distributed concentrated zwisohen 1.5 liters ether and 550 ml Viasser and the aqueous phase extracted again with 500 ml of ether. The combined ether phases are filtered through charcoal and, after drying, with anhydrous Na ₂ SO. concentrated under reduced pressure. This gives 178.3 g = 90.3 # d. Th.

909881/1709 ..- 11-

- «* ώ - ÖAO QRIßll ^ AL

crude l — ii— ¹ Irxyl-J, Γ, ^r ), (> .- - · - · ■ ·: rahydro-T-pyridylcarbinol ₉ which can be used for esterification without further *. · purification «

l-Isoamyl-1,2,5? 6-tetrahydro ~ 3

18.4 g (0.1 mol) 1 ^ TgoaEyl-ljSjSf6 ~ t £ tra * iydro ~ 5 ~ pyridyicarbinol and 10 _s 2 g (O ₉ I Hol) of absolute triethylamine are dissolved in 100 μl of absolute benzene. With external cooling with ice water and stirring, a solution of _{26.5 g (O 5} I mol) of α, α-diphenyl-achloroacetyl chloride in 100 ml of absolute benzene solution is added dropwise to this solution over the course of 20 minutes. Stirring is continued for an hour at room temperature, the triethylammonium chloride is filtered off with suction and the solution is concentrated in the yakuuin. The oily residue is boiled in 200 ml of distilled water. After a clear solution has formed (about 5 minutes), a pH of 5 - 6 is set with 2 η hydrochloric acid, cooled and shaken out several times with small portions of ether. The aqueous phase was made alkaline with salt carbonate solution and extracted three times with 50 ml of ether each time. Hach / ffÄ TröJcniii, $ ber K ^ Cp ,. * ri5ffl dejr.lther

and converted into the hydrochloride with alcoholic hydrochloric acid (pH 3 - 4). The alcoholic solution of the hydrochloride is filtered through charcoal and ether is added until the onset of turbidity. Yield: 19 g of 1-isoamyl-1,2,5,6- tetrahyaro- pyridyimethylbenesilic acid ester * - 45 ^ d. Th. From mp. 151-152 ⁰ C.
»Hydrochloride 9 09881/1709 - 12 -

Example 3

ln-hexyl - 1,2,5 _y 6-tetrahyciro-3-pyridy lmethylbenzilic acid ester methanesulfonate (according to method b) 32.34 g (0.1 mol) 1,2, S ^ -Tetrahydro-S- pyridylmethylbenzilsäureester and 18.2 g (0.11 mol) 1-ri-bromohexane are refluxed for 5 hours in 75 ml of absolute benzene in the presence of 11 "1 g (0.11 mol) of absolute triethylamine and left at room temperature for 15 hours. The triethylammonium bromide which has crystallized out is filtered off with suction and the filtrate is largely concentrated in a water jet vacuum at a maximum external temperature of ^{50 ° C.} The residue is dissolved in 50 ml of alcohol, adjusted to pH 2 with methanesulfonic acid and mixed with ether until it becomes cloudy.

Yield: 31 g = 61.5 % of theory . Th. Of m.p. ^{141-142 0} C. Bromoethylate m.p. 177-178 ⁰ C.
Bromobutylate m.p. 144-145 ° C

Example 4

1-.beta. (Met hoxyäthyl) -1 _T 2 _f 5 _T 6-tetrahydro-3 ~ pyrldylmethyI-benzil-hy ~ säureester hydrochloride (after yerfahren _m ^ JpJl ₁ 32.3 g (0.1 mole) of 1,2, 5,6-Tetrahydro-3-pyridyl-methyl-benzilic acid esters are dissolved in a mixture of 75 ml of tetrahydrofuran and 30 ml of dimethylformamide while warming to about 50 ° C. and 16.8 g (0.2 mol) of anhydrous sodium bicarbonate are added and reflux are within half an hour 15.3 g (0.11 mol) of 2-ß- (bromoethyl) methyl ether, dissolved in 15 ml of tetrahydrofuran, and 6 ml of dimethyl ·

- 13 - 909881/1709

formamide was added dropwise. After four hours of refluxing, inorganic material is suctioned off and the filtrate is largely concentrated in a boiling water bath under a water jet vacuum. The residue is dissolved in 30 ml of benzene, filtered through activated charcoal and concentrated again then on a silica gel column, each with ethyl acetate as the mobile phase. The eluates are in a water jet vacuum at a Badteaperatur of 50 ⁰ C eingeengtο yield of base ι 2O _5, 15 g - 54.4% d "Th * hydrochloride mp. 145 - 146 ⁰ C.

l ^ t ^ i ^

^ p Jjij g ^ terj ^ h ^ drQcMorid ^ Jjiach ¥ ejg | hr en a ) ^ To a solution of 14 "1 g (0 _p l mol) l ~ ethyl-l ₅ 2p5p6- = tetrah ¥ dro- ~ 3- PTriöylcarbinol and 10 _s 2 s absolute triethylamine in 100 ml of anhydrous benzene are added dropwise within 30 minutes with stirring and cooling a solution of 22.3 g (0 ^ 1 mol) of ot-cyclopeatyl-ot-phenylacetic acid chloride in 100 ml of absolute benzene ο Es the mixture is stirred for two hours at room temperature, the precipitated triethylammonium chloride is filtered off with suction IUId _1, the bengolic solution is concentrated in vacuo. The residue is mixed with water, weakly acidified with 2 η hydrochloric acid and extracted twice with a little ether. The acidic solution is made alkaline with NaHCO 3 and extracted with ether. The ethereal solution, dried with anhydrous sodium sulfate, is concentrated in vacuo and the crude base in the usual way

90988 1/1709. -14-

Way into the hydrochloric! convicted. By recrystallization from acetonitrile / ether one obtains 23 g = 63, ^ ^ d. Th. Des analytically pure salt with a melting point of 166 - 168 ° C.

909881/1709

- ULs 1929S21

According to the method described above, the receive the following connections:

CH "- 0

It

R,

C-R-

R /

example

R /. salt

CH ₂ -CH ₃ OH C ₆ H _r C ₆ H ₅ HCl

Mp. ⁰ C

163

CH ₂ -CH ₃

OH C ₆ H ₅ bromoethylate 190-191

CH (CH ₃ ) ₂

13 (CH ₂ ) ₇ CH ₃

14 (CH ₂ )

16 CH ₂ CH = CH,

17 CH ₂ CH = CHCl

OH C ₆ Ii ₅

^{0H C} 6 ^H 5 ^C 6 ^H 5

10 (CH ₂ ) 3 ^CH 3 OH ^C 6 ^H 5 11th (CH ₂ ) 4 ^CH 3 OH ^C 6 ^H 5 12th (CH ₂ ) 6 ^CH 3 OH ^C 6 ^H 3

OH C ₆ H ₅ C ₆ H ₅

OH C ₆ H ₅ C ₆ H ₅

OH C ^ Hk

OH C ₆ H ₅ C ₆ H ₅

OH

HCl 131 HCl 167-168 HCl 143 HCl 150 HCl 140 HBr 125 - HBr 124 HCl 127 HCl 143-144 HCl 135

0 988-1 / 1

Example R ₁ ^R 2 ^R 3 ^R 4 salt m.p. ⁰ C

18 CH ₂ CH ₂ C ₆ H ₅ OH C ₆ H ₅ C ₆ H ₅ HCl. 172-173

19 CH ₂ -CH ₃ H cyclohexyl C ₆ H ₅ HCl 203-204

20 CH ₂ -CH ₃ cyclopentane. C ₆ H ₅ HCl 143-145

21 CH ₂ -CH ₃ Cyclohexane ^C 6 ^H 5 ^C 6 ^H 5 HCl 186-188 22nd CH ₂ -CH ₂ -CN OH C ₆ H ₅ ^C 6 * 5 HCl 146-148 23 CHo-CSCH ^v OH C ₆ H ₅ ^C 6 ^H 5 HCl 142-143 24 CH ₂ -CH ₃ OH ^C 6 ^H 5 Cyclo
hexyl HCl 210-212 25th (CH ₂ ) ^ - CH ₃ OH C ₆ H ₅ Cyclo
hexyl HCl 132-135 26th CH ₂ -CH ₃ H ^C 6 ^H 5 HCl 198-200

909881/1709

Examples of pharmaceutical use

a) Dragejys

1 coated tablet contains?

1-n-hexyl-l, 2,5, 6-tetrahydro-3-pyridylmethyl-lbeazilsäureester. "- HCl lactose corn starch gelatin Magnesiuiastssrat

hex s division; ßv

The. Cluing of the irksubstoff with Illlchzucker and Ilaisut starch is carried out with an aqueous gelatin solution by a Jieb with 3 me; Granulated ash-width, dried at 40 ° and rubbed through a sieve again. The granules obtained in this way are mixed with magnesia stearate and pressed v / aqueous suspension of sugar, titanium dioxide, talc "nd Gu.mr;. arabicum is applied _c Lis finished coated tablets are polished with beeswax iirag'ae - snd. weight; 100 n: g

-i! "Chyj. · = ·.! j, 2, 5 · 6 - == 'üi

soluble starch kagnesium stearate

HCl

J mg 50 mg -32 ag IBg 1 mg 90 mg

Active ingredient m; d! '! AgnesiuBistear-at are with an aqueous Solution of the soluble starch granulated, the granules dried and intimately mixed with lactose and I; aisstarkks. The mixture is then compressed into tablets weighing 90 mg each containing 3 mg 7 / active substance «,

BATH ORIGINAL

9 0 9 8 8 '1/1 7 0 p

- 19 ■ -

1 zajichen contains;

1-AlIyI-I ₅ ? » 5, b-tetrahydro-2-

pyrLdylm "thyl ~ benzi! säureester" HCl 5 mg O ₉

Suppositories 1695 ₉ 0 mg

170O ₉ O mg

Manufacturing -

The feinverrulverte substance is stirred by means of an immersion into the molten liomogenisators and 40 ⁰ C cooled Zäpfchenraasse. The mass is poured into slightly pre-cooled molds at 35 C »

_d l_Amjrul 1 en

1-II-Hexyl =!, £, 5 ₅ fi = tetrahy-iro-3-pyridylethyl-benziisä-jr.e-ester _β HCl 2.0 mg

fiatric chloride 18.0 ι: ψ -

distilled water to 2.0 ml

Manufacturing c

Natritimchlorid active ingredient and are dissolved in water, releases the solution of suspendie - + sn filtered particles and in 2 cc-Ami-Ullen under sep &"isehen conditions bottled" Last "the Ampu, closed x ~ n ~ ver and sterilized. Each ampoule contains 2 mg of active ingredient,

BAJ) 9 0 9881/1709 "'

Claims (1)

1. New 1-AHkyl-1,2,5,6-tetrahydro-3-pyridylmethyl-carboxylic acid ester the general formula OR ₀ If / ² CH ₀ -0-CC-- R, ^R 4 wherein R _{1 is} an alkyl radical with 2-10 carbon atoms which is optionally substituted by a cyano or alkoxy group, a branched alkyl radical with 3-5 carbon atoms, an alkenyl radical with 2-3 carbon atoms optionally substituted by a halogen atom, an alkynyl radical with 2-3 carbon atoms, a cycloalkyl group with 3-6 carbon atoms or a phenylalkyl group Rp hydrogen, methyl, the hydroxy group or a ^ chloro atom, R ^ hydrogen, the phenyl or a cycloalkyl group with 5-6 carbon atoms or R ₀ and R-, together a 5- or 6-membered cycloaliphatic ring and R ^ a phenyl group, where, if R, and R ^ each represent a phenyl ring, these rings are optionally in the o-position to the point of attachment with the <xC atom of acetic acid by a direct bond or via an oxygen atom, as well as their acid addition salts and quaternary ammonium compounds. 909881/170 9 2. New-l-alkyl-1, 2, b , b-tetrahydro-T-pyridylmethylbenzilic acid ester of the general formula wherein K ^ is an alkyl group having 2-6 carbon atoms or the Alt ίgruppe means and their acid addition salts and quaternary ammonium compounds. Ο 3-hexyl ln = l _s 2j, 5 _s 6-tetrahydro-3-pyridylmethyl-benzilic soi ^ ie its acid addition salts and ammonium compounds .quaternär © " ο 1-ethyl-1 ₉ 2.5 s, 6-tetrahydro-3-pyridylmethyl-benzilic acid ester and its acid addition salts and qua ternary ammonium compounds ,, !, 2.5 ₉ ö ^ -feetrahydro ^ -pyridylraetliyl-benzil säureestsr and its acid addition salts and ammonium compounds cpaternäre _o β ο l = Plienylätliyl- = l ₉ .2 ₉ 5 ₈ 6- = tetrahydro ~ 3 = pyridy! methyl »" bensilsäwreester sox ^ ie its -Saureadcliijioassalss- 7. l-Allyl-l _s 2.5i> 6-t3trahydro-3-pyridylmethylben2il3 acid ester and its acid addition salts and quaternary ammonium compounds * 8. Process for the preparation of new 1-alkyl-1,2,5,6-tetrahydro-3-pyridyliaethyl-carboxylic acid esters the general formula 0 .R ₀ CH ₀ 0 "- C - C - FU wherein R-. iron given snf fells by elae Cyeac or Alk-02sygruppe substitution; ea -.Ikylrest old 2-10 carbon = · atoasn »; elnea ver ^ weigtss / rl'rv'l ^ & sit with 3-5 carbon atoms: -. j. An alkali radical salt 2 - 3 carbon atoms, an alkali radical with 2-3 carbon atoms, a cycloalkyl radical with 3—6 carbon atoms, or © ineia Phsnylalliyl- Hydrogen j methyls άχο Hyd.ros: ygryppe 'or © in Ciiloi f, the phenyl or a. Cycloalkyl radical with 3-6 carbon atoms or R ₂ and FU together form a 3- or 6-membered cycloaliphatic ring and R ^ a pheayl radical »where, when R 1 and R ^ ^ e represent a phenyl ring, these rings optionally in 90 9 881/1709 ß to the connection point with the; a-G-atoin of acetic acid are linked to one another by a direct bond or via an oxygen atom, be as well as "their acid addition salts and quaternary ammonium compounds, characterized in that one a) a compound of the general formula CH ₂ -X wherein R- has the meaning given above and X represents the hydroxyl group or a halogen atom, with a compound of the general formula R ₂ 0 C-C = Y where R? 9 R ^ ^{un (} 3 IX. Have the meaning given above and Y denotes the hydroxyl or an alkoxy group or a metal, bsv; ₀ another derivative of this compound suitable for esterification is esterified by processes known per se, or that one 909881/1709 BATH ORIGINAL b) an ester of the general formula '929321 V * 0 Air y 2 Il / CH ₉ O - C - C - R * ^R 4 N I ■ where Rp, R, and R. have the meaning given above ^ "own, on the nitrogen atom of the tetrahydropyridine ring is alkylated by processes known per se and that the compounds thus obtained are, if appropriate, alkylated of the general formula I in the usual way in their physiologically acceptable acid addition salt . and quaternary ammonium compounds η Pharmaceutical preparations containing as active ingredient y · one or more compounds of the general formula I or their physiologically acceptable acid addition salts or quaternary ammonium compounds in combination with customary auxiliaries and / or carriers. Io. Pharmaceutical preparations containing as active ingredient one or more compounds of the general formula I or their physiologically acceptable acid addition salts or quaternary ammonium compounds in combination with other active pharmaceutical ingredients 209881/1709 as well as with the usual auxiliaries and / or carriers. 11. Pharmaceutical preparations containing as active ingredient one or more compounds of the general formula I or the physiologically acceptable ones Acid addition salts or quaternary ammonium compounds in a dose of 0.1-50, preferably 1-5 mg. 909881/1709