KR840002433B1 - Process for preparing n-substituted derivatives of tetrahydropyridyl indole - Google Patents

Abstract

The title cmpds. [I; X = C1-6 alkyl, C4-7 cycloalkyl, C2-5 hydroxyalkyl or C1-5 phenoxyalkyl; R = H, halogen, nitro, amino or methylthio; R1,R2 = H were prepd. by the reaction, of II and Hal-X[X = X' or X"; X' = tetrahydropyranyloxyalkyl; X" = C1-6 alkyl, C5-6 cycloalkylthio 3-(1,2,3,6-tetrahydro-4-pyridyl)-1Hindole HCl salt, 4.2cm3 propyliodide, 6g sodium carbonate and 160cm3 dimethylformamide was stirred for 4 hrs. and crystallized to give 5.2 g 5-methyltio-3-(1-propyl-1,2,3,6-tetrahydro-4-pyridyl)1H-indole HCl salt.

Description

Method for preparing N-substituted derivatives of tetrahydropyridyl indole

OBJECT OF THE INVENTION The present invention relates to a process for preparing salts of N-substituted derivatives of novel tetrahydropyridyre-phosphines of the general formula (I) with inorganic or organic acids thereof:

Wherein X is an alkyl group containing 1-6 carbon atoms, a cyclokalkyl group containing 5 or 6 carbon atoms, a cycloalkyl group containing 4-7 carbon atoms, an alkenyl group containing 2-5 carbon atoms, 3 An alkynyl group containing 5 carbon atoms, an aralkyl group containing 7-12 carbon atoms, a hydroxyalkyl group containing 2-5 carbon atoms or an phenoxy alkyl group containing 1-5 carbon atoms R represents a hydrogen or halogen atom or an alkoxy group containing 1-3 carbon atoms, natro, amino, trifluoromethyl or methylthio group, R ₁ and R ₂ represent a hydrogen atom or 1-3 carbon atoms X represents a hydrogen or halogen atom or an alkoxy group containing 1-3 carbon atoms. To burn.

In general formula (I), an alkyl group containing 1-6 carbon atoms represents, for example, a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl or isopentyl group and is a cyclo containing 5 or 6 carbon atoms. Alkyl groups represent cyclopentyl or cyclohexyl groups, cycloalkyl groups containing 4-7 carbon atoms, for example, cyclopropylmethyl groups, alkenyl groups containing 2-5 carbon atoms, for example, vinyl, allyl, An alkynyl group containing 3-5 carbon atoms, for example a propargyl group, an aralkyl group, for example a benzyl or phenethyl group, and an alkyl group A hydroxy alkyl group containing 2-5 carbon atoms is, for example, hydroxyethyl, hydroxypropyl, for example phenoxymethyl, phenoxyethyl, pen A propyl, phenoxybutyl or phenoxypentyl group, a halogen atom may be a fluorine, chlorine or bromine atom, and an alkoxy key containing 1-3 carbon atoms represents, for example, methoxy, ethoxy or propoxy group , Alkyl group containing 1-3 carbon atoms represents, for example, methyl, ethyl or propyl group.

The substituent R may be at any position on the indole ring, but preferably at position 5 or 6, particularly at position 5.

Addition salts with inorganic or organic acids are, for example, hydrochloric acid, bromic acid, nitric acid, sulfuric acid, phosphoric acid, acetic acid, formic acid, propionic acid, benzoic acid, maleic acid, fumaric acid, succinic acid, tartaric acid, citric acid, oxalic acid, glyoxylic acid and aspartic acid. Salts formed with alkanesulfonic acids such as methane or sulfonic acid, arylsulfonic acids such as benzene or paratoluenesulfonic acid and aryl carboxylic acids.

Among the products obtained by the present invention, mention may be made in particular of derivatives of the general formula (I), as well as addition salts thereof with inorganic or organic acids, the characteristic being that X is an alkyl group in the general formula (I). Represents a hydroxyalkyl group containing 2-5 carbon atoms and R, R ₁ and R ₂ are as described above. In addition, the feature is that X represents a phenoxyalkyl group in which the alkyl group contains 1-5 carbon atoms, R, R ₁ and R ₂ are as described above, and in addition to this feature, X contains 1-6 carbon atoms. An alkyl group, a cycloalkyl group containing 5 or 6 carbon atoms, a cycloalkylalkyl group containing 4-7 carbon atoms, an alkenyl group containing 2-5 carbon atoms, an alkynyl group containing 3-5 carbon atoms or 7- Aralkyl groups containing 12 carbon atoms may be mentioned and R ₁ and R ₂ may be mentioned derivatives corresponding to the general formula (I) and their addition salts with inorganic or organic acids.

Among the derivatives obtained by the present invention, the derivatives described in the examples and in particular 5-nitro-3- (1-propyl-1,2,3,6-tetrahydropyrid-4-yl) -1H-indole Hydrochloride may be mentioned.

The method for preparing derivatives of general formula (I) is characterized as follows.

(a) reacting the product of formula (II) with a halide of formula (III) to obtain a derivative of formula (V), hydrolyzing it to give the desired compound, and if necessary reacting with an acid to To obtain the product of formula (I) wherein X to obtain a salt represents a 2 to 5 carbon atom-containing alkyl group, or Hal-X '(III)

In the above formula

일반식의 테트라히드로 피라니옥시-알킬기를 나타내고 n은 2,3,4 또는 5의 정수를 나타내며,R, R ₁ and R ₂ are as described above and Hal represents a chlorine, bromine or iodine atom where X is X 'and X' is

A tetrahydro pyranoxy-alkyl group of the general formula and n represents an integer of 2,3,4 or 5,

(b) reacting the product of formula (III) with a halide of formula (III) to separate the product and, if necessary, with an acid to obtain its salts:

Hal-X ″ (Ⅲ)

Wherein Hal represents a chlorine, bromine or iodine atom and in formula (III) X is X ″ and X ″ is an alkyl group containing 1-6 carbon atoms, a cycloalkyl group containing 5 or 6 carbon atoms, 4 A cycloalkylalkyl group containing 2 carbon atoms, an alkenyl group containing 2-5 carbon atoms, an alkynyl group containing 3-5 carbon atoms an aralkyl group containing 7-12 carbon atoms or an alkyl group containing 1-5 carbon atoms The phenoxyalkyl group containing is shown.

Under the conditions for carrying out the invention, the characteristics of the process for preparing the derivatives of general formula (I) are as follows.

The reaction of the product of formula (II) with a halide of formula (III) (where X represents X ') is carried out in an organic solvent such as isobutylmethylketone in the presence of sodium carbonate.

Hydrolysis of the product of general formula (V) is carried out using a hydrochloric acid solution in an alkanol such as methanol or ethanol.

The reaction of the product of formula (II) with a halide of formula (II) (where X represents X ") is carried out in an organic solvent such as dimethylformamide in the presence of sodium carbonate.

The reaction can also be carried out in acetone or isobutylmethylketone in the presence of sodium carbonate of silver triethylami.

Derivatives of formula (I) are essentially basic. Addition salts of the derivatives of formula (I) with acids can be advantageously prepared by reacting the inorganic or organic acids with derivatives of formula (I) in a substantially stoichiometric ratio. Salts can be prepared without separating the bases.

The derivatives of the present invention have very interesting pharmacological properties, and in particular, they have excellent neuropathy, psychopathy and anti-erosion properties.

These properties are further illustrated in the experimental section. Due to this property, tetrahydropyridyl-indole-N-substituted derivatives of general formula (I) as well as their pharmaceutically acceptable salts can be used as pharmaceuticals.

Among the pharmaceutical products according to the present invention, these compounds are characterized in that X represents a hydroxyalkyl group having an alkali group containing 2-5 carbon atoms, and R, R ₁ and R ₂ correspond to the general formula (I) as described above. New N-substituted derivatives of tetrahydropyridyl-indole and their addition salts with pharmaceutically acceptable acids, and X represents a phenoxyalkyl group in which the alkyl group contains 1-5 carbon atoms; ₁ and R ₂ are addition salts with the compounds corresponding to general formula (I) as described above and their pharmaceutically acceptable acids, and X is an alkyl group containing 1-6 carbon atoms, 5 or 6 A cycloalkyl group containing 4 carbon atoms, a cycloalkylalkyl group containing 4-7 carbon atoms, an alkenyl group containing 2-5 carbon atoms, an alkynyl group containing 3-5 carbon atoms or 7-12 carbon atoms doing An aralkyl group, R represents a nitro, amino, trifluoromethyl or methylthio group, R ₁ and R ₂ represent compounds corresponding to general formula (I) as described above and their pharmaceutically acceptable acids Consists of addition salts.

Among the medicines according to the invention, in particular the following derivatives are included.

5-nitro-3- (1-propyl-1,2,3,6-tetrahydropyrid-4-yl) -1H-indole hydrochloride.

The medicines according to the invention are used, for example, in the treatment of psychological, behavioral and personal diseases as well as in the treatment of vomiting and nausea.

Typical dosages may vary depending on the derivative used, the person being treated and the disease involved and may be 5-200 mg per day, for example in oral use in adult men.

Derivatives obtained according to the present invention can be used to prepare pharmaceutical compositions containing as active active ingredient at least one of the aforementioned derivatives or addition names with pharmacologically acceptable acids thereof.

Derivatives of the general formula (I) as a medicament and their addition salts with pharmacologically acceptable acids can be mixed with pharmaceutical compositions for digestive or oral administration.

These pharmaceutical compositions may be solid or liquid, for example, and may be prepared in the form commonly used in medical drugs such as extruded dragees, gelatin capsules, granules, suppositories and injections. These are prepared by known methods. The active ingredients are talc, gum arabic, lactose, starch, magnesium stearate, cocoa butter, aqueous or non-aqueous bases, animal or vegetable fats, paraffin derivatives, glycols, various wetting agents, dispersions or It may be mixed with excipients such as emulsifiers and preservatives.

The product of formula (II) may be prepared by reaction of the product of formula (VI) with 4-piperidone hydrochloride, if not known,

(Wherein R, R ₁ and R ₂ are as described above)

This reaction is preferably carried out in an alkaline medium and if R represents an alkyl group it is preferably carried out in an acid medium.

Under the conditions for carrying out the invention, the reaction of the product of general formula (VI) with 4-piperidone hydrochloride is carried out in 2N methanolic potassium hydroxide. Examples of such manufacturing methods are mentioned later in the experimental section.

The product of formula (VI), wherein R represents a methylthio group, can be prepared by reacting a copper mercaptate with an indole of the following formula (VII).

Examples of such manufacturing methods are mentioned later in the experimental section.

Hereinafter, the present invention will be described in more detail with reference to the following Examples.

Example 1

5-Methylthio-3- (1-propyl-1,2,3,6-tetrahydro-4-pyridyl) -1 H-indole hydrochloride

A suspension in which 7 g of 5-methylthio 3- (1,2,3,6-tetrahydro-4-pyridyl) -1H-indole, 6 g of sodium carbonate and 4.2 cm 3 of propyl iodide are dissolved in 160 cm 3 of dimethylformamide This is stirred for 4 hours at room temperature. The mixture obtained at the end of the reaction is poured into water, filtered, washed with water and dried.

7.1 g of yellow crystals were liberated, which was recrystallized from isopropanol to give 6 g of yellow crystals having a melting point of 176 ° C.

Preparation of hydrochloride:

5 g of base are placed in a suspension in 300 cm 3 of ethyl acetate, the suspension is cooled to 0-5 ° C., ethyl acetate solution is added, the mixture is filtered, washed with ethyl acetate, the mixture is filtered, ethyl acetate After washing with water and drying to recrystallize from a mixture of 500 cm 3 of isopropinol and 100 cm 3 of methanol, 5.2 g of yellow crystals of 23 ° C. are obtained.

analysis :

C ₁₇ H ₂₂ N ₂ S HCl = 322.9

The starting material, 5-methylthio-3- (1,2,3,6-tetrahydro-4-pyridyl) -1H-indole may be prepared as follows.

a) 5-methylthio-1H-indole

22.7 g of 5-bromo-1H-indole was stirred for 5 hours with 230 cm 3 of quinoline, 34 cm 3 of anhydropyridine and 16 g of 16 g prepared according to FNGELHARDT J. Med. Chem. II 329 (1968). Reflux with copper methyl mercaptate: The mixture is cooled and precipitated 2N in 1 liter of 2N hydrochloric acid and 1 liter of ethyl acetate, filtered and decanted, washed with 2N hydrochloric acid and brine and dried, the solvent is 40 17.8 g of crude product was recovered by evaporation under reduced pressure at < RTI ID = 0.0 > C, < / RTI > which was purified by chromatography on silica and eluted as a cyclohexane and benzene mixture (1: 1) to afford 11.75 g of the desired product.

UV Spectrum in Ethanol

Infl: 250 nm = 710

Infl: 278 nm = 249

Infl: 294 nm = 188

Infl: 310 nm = 98

b) 5-methylthio-3- (1,2,3,6-tetrahydro-4-pyridyl) -1H-indole

The product obtained in the previous step is stirred under inert gas with 22.1 g of 4-piperidone hydrochloride and 108 cm 3 of 2N methanolic potassium hydroxide, the resulting suspension is refluxed and cooled for 16 hours, and the mixture is obtained with 1 liter After poured into water, stirred for 15 minutes, filtered, washed with water and dried to recrystallize from a mixture of ethyl acetate and methanol (10: 3) to give 14.8 g of yellow crystals having a melting point of 210 ° C.

Example 2

5-nitro-3- (1-propyl-1,2,3,6-tetrahydropyrid-4-yl) -1H-indole hydrochloride

11.2 g of 5-nitro-3- (1,2,3,6-tetrahydropyrid-4-yl) -1H-indole hydrochloride was mixed with 140 cm 3 of 6.4 cm 3 of 6.4 cm 3 iodide propyl and 12.72 g of sodium carbonate. The mixture is stirred under inert gas for 5 hours 30 minutes, the mixture is diluted with 300 cm 3 of distilled water, crystallized, stirred for 1 hour, separated, washed with water and then washed with 25 cm 3 of 50% ethanol and dried. 11.5 g of crystals at 164 ° C. were recovered, which was chromatographed on silica and eluted with a mixture of chloroform and acetone (8: 2). 9.5 g of crystals having a melting point of 172 ° C are obtained.

Preparation of hydrochloride:

The obtained 6.13 g base is added to the suspension in 150 cm 3 ethanol, the suspension is cooled, hydrochloride ethanol is added until pH = 1 under stirring, the mixture is stirred for 40 minutes under inert gas, separated and ethanol After washing and drying, the desired 6.90 g of product was recovered, which was recrystallized from ethanol containing 20% water. 5.85 g of crystals having a melting point of 240-242 ° C. are obtained.

analysis :

_{C 10 H 19 N 3 O 2} · Hcl: 321.814

5-nitro-3- (1,2,3,6-tetrahydropyrid-4-yl) -1H-indole hydrochloride can be prepared as follows.

7.7 g of 5-nitro-1H-indole was refluxed under nitrogen gas for 3 hours with 225 cm 3 of ethanol saturated with hydrochloric acid and 22.5 g of hydrated 4-piperidone hydrochloride, and then the mixture was allowed to stir at room temperature for 1 hour and 0 ° C. After stirring for 1 hour at filtration, washing with cold ethanol, ethyl acetate and ether, 14 g of the desired crude product are obtained.

14 g of the obtained product was recrystallized from 600 cm 3 of a mixture of methanol and water (1: 1), then left at 0 ° C. and + 5 ° C. overnight, filtered, washed with methanol and dried to 9.5 having a melting point of 275 ° C. g of the desired pure product are obtained.

analysis :

C ₁₃ H ₁₄ CIN ₃ O ₂ = 279.733

Example 3

3- (1-propyl-1,2,3,6-tetrahydropyrid-4-yl) -1H-indol-5-amine hydrochloride

Using the same method as that used to prepare the product of Example 1, 5-aminoin as starting material is 2,3- (1-propyl-1,2,3,6-tetrahydropyrid-4 -Yl) -1H-indole-5-amine hydrochloride is prepared. Melting point = 265 ° C

analysis :

C ₁₂ H ₂₂ N ₃ Cl = 291.891

Example 4

5-chloro-3- [1- (2-phenoxyethyl) -1,2,3,6-tetrahydropyrid-4-yl] -1H-indole hydrochloride

7.5 g of sodium carbonate and 9 g of β-bromine dissolved 8 g of 5-chloro-3- [1,2,3,6-tetrahydropyrid-4-yl] -1H-indole in 80 cm 3 of dimethylformamide After stirring for 2 hours under inert gas with mofetol, it is cooled at room temperature and standing up dilute with 400 cm 3 of distilled water, stirred for 30 minutes, separated, and then with water and then with a mixture of ethanol and water (1: 1) After washing and drying 14 g of crude product is recovered.

15.8 g of the product as previously obtained are purified by chromatography on a silica column and eluted as a mixture of chloroform, acetone, triethylamine (6: 3: 1). The product obtained is recrystallized from ethanol to give 11.53 g of product having a melting point of 172 ° C.

Preparation of hydrochloride:

The product obtained above is added to a suspension in 500 cm 3 of ethanol, dropwise until the hydrochloric ethanol solution is brought to acidic pH and the precipitate is redissolved by heating, the resulting solution is filtered, concentrated in half and crystallized The crystals are separated, washed with ethanol and dried. 12.1 g of product having a melting point of 190 ° C. are recovered, which is recrystallized from ethano to yield 9.25 g of product which is melted at 180 ° C. and then melted at 220 ° C.

analysis :

C ₂₁ H ₂₂ Cl ₂ N ₂ O = 389.3

The starting material, 5-chloro-3- (1,2,3,6-tetrahydropyrid-4-yl) -1H-indole, can be prepared as described in French Patent No. 2,362,628.

Example 5

Neutral Oxalate of 4- (1H-Indol-3-yl) -3,6-dihydro-1- (2H) -pyridyl ethanol

Step A: 3- [1 (2- (2-tetrahydro pyranyloxy) -ethyl] -1,2,3,6-tetrahydro-pyrid-4-yl] -1H indole

6.93 g of 3- (1,2,3,6-tetrahydropyrid-4-yl) -1H-indole dissolved in 70 cm 3 of isobutyl methyl ketone at 100 ° C. (described in French Patent No. 2,362,628) Silver was refluxed with 11.13 g of sodium carbonate and 14 cm 3 of 2-[(2-chloroethyl) -oxy] -tetrahydro-2H-pyran for 5 hours and 30 minutes under stirring and inert gas, then cooled and poured into ice water. .

Extraction with ethyl acetate, washing with water and brine, drying and evaporation to dryness recover 9.9 g of crystals which are purified by chromatography on silica (eluent: chloroform, acetone, triethylamine, 85). : 10: 5) A 7.85 g crystal having a melting point of 135 ° C. was obtained.

Step B: Neutral oxalate of 4- (1H-indol-3-yl) -3.6-dihydro-1- (2H) -pyridyl ethanol

The product obtained in the previous step is added to 156 cm 3 of 95 ° C. ethanol, 15.6 cm 3 of 6N hydrochloric acid is added, the mixture is stirred under inert gas for 3 hours 30 minutes, and the resulting mixture is poured into 1 liter of water, 10 3 cm 3 of sodium hydroxide solution is added, the admixture is filtered and the crystals thus obtained are washed with water. It is dried under reduced pressure and 4.068 g of crystals having a melting point of 164-165 캜 are obtained.

Preparation of neutral oxalate:

The 3.815 g product obtained earlier is dissolved in 200 cm 3 of ethanol, 992 mg of oxalic acid is added, and the obtained crystals are redissolved in 1.5 liters of ethanol under reflux, which is heated and filtered and the solution is concentrated and slowly crystallized. , Isolated and washed with ethanol to give the desired 3.245 g of product having a melting point of 197-200 ° C.

analysis :

C ₃₂ H ₃₈ N ₄ O ₆ = 574.683

Example 6

3- (1-cyclopropylmethyl) -1,2,3,6-tetrahydro pyrid-4-yl-5-nitro-1H-indole hydrochloride

11.88 g of 5-nitro-3- (1,2,3,6-tetrahydro pyrid-4-yl) -1H-indole hydrochloride has 148 cm 3 of dimethylformamide, 12.72 g of sodium carbonate and 4.8 cm 3 of chloromethyl Stirred at about 70 ° C. under inert gas with cyclic propane, the mixture was cooled, 450 cm 3 of distilled water was added, the mixture was stirred for one hour, separated, washed with water and dried to recover 10.8 g of crude product. This was chromatographed on silica (eluent: chloroform, acetone, triethylamine, 6: 3: 1), giving 8.3 g of the desired product having a melting point of 187-188 ° C.

Preparation of hydrochloride:

8.7 g of base obtained in the previous step is added to a suspension in 130 cm 3 of ethanol, the suspension is cooled, hydrochloric ethanol is added under stirring until the pH is 1, the mixture is stirred under inert gas for 2 hours, Separation, washing and drying with ethanol yield 9.55 g of the desired product which is recrystallized from methanol. 7.2 g of crystals having a melting point of 253-255 ° C. are obtained.

Analysis: C ₁₇ H ₂₀ NClN ₃ O ₂ = 333.826

Calculated Value: C% 61.16 H% 6.03 Cl% 10.62 N% 12.58

Experimental value: 61.5 6.1 10.9 12.4

Example 7

Neutral oxalate of 4- (5-chloro-lH-indol-3-yl)-(1,2,3,6-tetrahydro-1- (2H) -pyridylpropanol

Step A: 3- [1- [3- (2-tetrahydro pyranyloxy) -propyl] 1,2,3,6-tetrahydropyridin-4-yl] -1 H-indole

11.6 g of 5-chloro-3- (1,2,3,6-tetrahydropyrid-4-yl) -1H-indole dissolved in 120 cm 3 of isobutyl methyl ketone was dissolved in 15.9 g of sodium carbonate and 22 cm 3 of It is heated to 100-105 ° C. for 24 hours under stirring and inert gas with 3-[(3-chloropropyl) -oxy] -tetrahydro-2H-pyran, then cooled and poured into 500 cm 3 of water.

The mixture is stirred for 1 hour, extracted with ethyl acetate, washed with water and brine, dried and evaporated to dryness to recover 29.6 g of crystalline product which is purified by chromatography on silica (eluent: chloroform, acetone, Triethylamine, 6: 3: 1) and 13.1 g of crystals having a melting point of 161 占 폚 are obtained.

Step B: Neutral Oxalate of 4- (5-Chloro-1H-indol-3-yl) -1,2,3,6-tetrahydro-1- (2H) pyridyl-propanol

The product obtained in the previous step is added to 290 cm 3 of 95 ° C. ethanol and 71.5 cm 3 of 2N hydrochloric acid are added, the whole is stirred for 4 hours under inert gas, and the resulting mixture is poured into 500 cm 3 of water, which is sodium hydroxide liquid. And the crystals thus obtained are washed with water. It was dried under reduced pressure to give 7.7 g of crystal having a melting point of 161-162 占 폚.

Preparation of Neutral Oxalate

The previously obtained 7.7 g of the product is dissolved in 77 cm 3 of ethanol, a solution of 1.66 g of oxalic acid in 16 cm 3 of ethanol is added, the whole is stirred under inert gas, separated, washed with ethanol, and from distilled water Recrystallized, separated, washed and dried to yield 7.11 g of desired product with melting points of 195 ° C and 217 ° C.

Analysis: C ₃₄ H ₄₀ Cl ₂ N ₄ O ₆ = 671.627

Calculated Value: C% 60.80 H% 6.00 Cl% 10.55 N% 8.34

Experimental value: 60.7 6.0 10.8 8.2

Example 8

Compressed tablets were prepared having the following contents.

Example 9

Compressed tablets were prepared having the following contents.

Example 10

Compressed tablets were prepared having the following contents.

Claims (1)

Formula (I) is characterized by reacting a product of formula (II) with a halide of formula (III), with N-substituted derivatives of tetrahydropyridyl-phosphines and inorganic or organic acids thereof Method for preparing the addition salts of the.

Hal-X (III) In the above formula (I) X is an alkyl group containing 1-6 carbon atoms, a cycloalkylalkyl group containing 4-7 carbon atoms, a hydroxy alkyl group containing 2-5 carbon atoms, or a phenoxy alkyl group containing 1-5 carbon atoms Represents an alkyl group, R represents hydrogen, a halogen atom, nitro, amino, or methylthio group, R ₁ and R ₂ represent a hydrogen atom, if R represents a hydrogen or halogen atom, X represents a C ₂ -C ₅ hydroxy alkyl or phenoxyalkyl group, Hal represents a chlorine, bromine or iodine atom, In Formula (III), X is represented by X 'or X ", and X' is a structural formula.

Phosphorus tetrahydropyranyloxy alkyl group wherein n is an integer of 2,3 or 4, and X "is an alkyl group containing 1-6 carbon atoms, a cycloalkyl group containing 5 or 6 carbon atoms, or an alkyl group A phenoxyalkyl group containing 1-5 carbon atoms is shown.