IL28530A - Quinoline-3-carboxylic acid ester derivatives - Google Patents

Quinoline-3-carboxylic acid ester derivatives

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Publication number
IL28530A
IL28530A IL2853067A IL2853067A IL28530A IL 28530 A IL28530 A IL 28530A IL 2853067 A IL2853067 A IL 2853067A IL 2853067 A IL2853067 A IL 2853067A IL 28530 A IL28530 A IL 28530A
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IL
Israel
Prior art keywords
stands
radical
carboxylate
ethyl
quinoline
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IL2853067A
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Ici Ltd
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Publication of IL28530A publication Critical patent/IL28530A/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
    • C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Quinoline Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Description

QUINOLINE-3-CARBOXYLIC ACID ESTER DERIVATIVES ϊ»7¾Λ*ιρ-3 nsoinn Ve? D'TOOK 7© nn?m η»7»ορκ:ηρ 28530/?' This invention relates to new qiiinoline derivatives which possess anti-coccidial activity.
According to the invention we provide qiiinoline derivatives of the formula: - 1 wherein X stands for an oxygen atom, R stands for an 2 alkyl radical, R stands for an W-octyl or N-dodecyl radical, or an aryloxyalkyl or aralkyl radical the aryl nucleus of either of which optionally bears one or more substituents selected from halogen atoms and alkyl, 3 alkoxy, alkylthio and nitro radicals, R stands for an 4 alkoxy or acyloxy radical, and R ffcstnds for hydrogen or an alkyl, alkoxy or alkenyloxy radical. suitable value for R there may be mentioned, for example, an alkyl radical of not more than 6 carbon atoms, for example the methyl, ethyl, . n -butyl radical. 28530/2 As a suitable value for R when it stands for an aryloxyalkyl or aralkyl radical, there may be mentioned, for example, an aryloxy- alkyl or aralkyl radical of not more than 15 carbon atoms, for example the B-phenoxyethyl, tu'-phenoxy- hexyl or benzyl radical. As suitable substituents 2 , which may be present on the aryl nucleus of R when it stands for an aryloxyalkyl or aralkyl radical, there may be mentioned, for example, chlorine and bromine atoms, and alky , alkoxy and alkylthio radicals of not more than 6 carbon atoms, for example methyl, methoxy and methylthio radicals, 2 and nitro radicals. Thus a specific value for R is, for example, the jp-methoxybenzyl, JB-(£-methyl- phenoxy)ethyl, ^-(p-methylthipphenoxy)ethyl, jB> - ( -nitrophenoxy)ethyl or p-chlorobenzyl radical. 3 As a suitable value for R when it stands for an alkoxy radical there may be mentioned for example, an alkoxy radical of not more than 6 carbon atoms, for example the methoxy, ethoxy or n-butoxy radical, and as a suitable value for R 3 when it stands for an acyloxy radical, there may be mentioned, for example, an alkanoyloxy radical - ■-of..not more than 6 carbon atoms, for example the acetoxy or n-butyryloxy._radical.
As a suitable value for when it stands for an alkyl, alkoxy, alkylthio or alkenyloxy radical, there may be mentioned any such radical containing not more than 10 carbon atoms, for example the methyl, n-propyl, n-butyl, n-octyl, ethoxy, n-propoxy, isopropoxy, n-octyloxy, n- butylthio, allyloxy or 2-methylallyloxy radical.
A preferred value for is an alkyl or alkoxy radical of not more than 10 carbon atoms in the 6-position of the quinoline nucleus, for example the 6-methyl, 6-n- propyl, 6-n-butyl, 6-n-octyl, 6-ethoxy, 6-n-propoxy, 6- isopropoxy or 6-n-octyloxy radical, or an alkylthio or alkenyloxy radical of not more than 6 carbon atoms in the 6-position of the quinoline nucleus, for example the 6-n- butylthio, 6-allyloxy or 6-(2-methylallyl)oxy radical.
Preferred quinoline derivatives of the invention are, for example, methyl 7~benzyloxy-6-n-butyl-U-methoxy- quinoline-3-carboxylate, ethyl 7-benzyloxy-6-n-propoxy-U- acetoxyquinoline-3-carboxylate, ethyl 7-benzyloxy-6- isopropoxy- -acetoxyquinoline-3-carboxylate, ethyl 7- benzyloxy-6-ethoxy- -acetoxyquinoline-3-carboxylate, ethyl 7-n-dodecyloxy-6-- propoxy- -acetoxyquinoline-3-carboxylate, methyl 7-benzyloxy-6-allyloxy - -acetoxyquinoline-3- carboxylate, methyl 7-β-(ρ,-methylphenoxy)ethoxy-6-n- butyl- -acetoxy-quinoline-3-carboxylate, methyl 7-benzyloxy- 6-n-propyl- -acetoxyquinoline-3-carboxylate, methyl 7- benzyloxy-6-n-butyl- -acetoxyquinoline-3-carboxylate, 28530/2 ethyl 7-j>-chlorobenzyloxy-6 -n-propyl-4 -acetoxyquinoline-3-carboxylate ahd ethyl Gf-behzyloxy-6 -n-propoxy-4-n- butyryloxyquinoline - 3 -c arboxylate.
According to a further feature of the invention we provide a process for the manufacture of those : 1 · . ''· . '. ...'·. .. ' 3 of the quinoline derivatives of the invention wherein R stands for an alkoxy radical of the formula R 0-, which comprises the interaction of a halogeno compound of the formula: - wherein R , R , R and X have the meanings stated above, and Z stands for a halogen atom, with a salt of, the formula '- + 5 ■+· R O A , wherein R stands for an alkyl radical and A stands for a metal ion.
It is to be understood that in the above 1 5 procdss, the product obtained is such that R and R always represent the same alkyl radical.
As a suitable value for A+ there may "be mentioned, for example, the ion derived from an alkali metal, for example the sodium or potassium ion. As a suitable value for R-^ there may be mentioned an alkyl radical of not more than 6 carbon atoms, for example the methyl, ethyl or n-butyl radical.
The interaction may be carried out in a diluent or solvent, for example an alcohol of the formula R . OH, wherein R has the meaning stated above, and it may be accelerated or completed by the application of heat.
According to a further feature of the invention we provide a process for the manufacture of those of the quinoline derivatives of the invention wherein ^ stands for an acyloxy radical, which comprises the interaction of a hydroxyquinoline derivative of the formula wherein R , R , R and X have the meanings stated above, with an acylating agent.
As a suitable acylating agent there may be mentioned, for example, an acylating agent derived from an acid of the formula R^.COOH, wherein R^ stands for an alkyl radical of not more than 5 carbon atoms, for example the methyl or n-propyl radical. A suitable derivative of the above-mentioned acid is, for example, the acid anhydride.
The above interaction with an acid anhydride derived from an acid of the formula .COOH, may "be carried out in a diluent or solvent, conveniently an excess of the said acid anhydride, optionally in the presence of a salt of the corresponding acid of the formula R .COOH. The interaction may "be accelerated of completed "by the application of heat.
The halogeno compounds of the formula used as starting materials for the manufacture of the quinoline derivatives of the invention wherein thief Isld IdM^ll iMJc/ahl Iddd R3 stands for an alkoxy radical, may "be obtained, kkl Idl dddi ti./ kfok/v/ j from the corresponding -hydroxyquinoline derivatives by interaction with a phosphorus oxyhalide. The -hydroxyquinoline derivatives of the form used as starting materials for the preparation of the quinoline derivatives of the invention wherein R^ stands for a halogen atom or an acyloxy radical, may be obtained by the cyclisation of the anil of the formula:- using the conventional thermal or phosphorus oxyhalide methods. Specific examples of such cyclisations are described in U.K. patent specification No. 1 , 070 , 223 » and descriptions of the preparation of all the individual 1+-hydroxyquinoline derivatives used as starting materials in the Examples, and not described therein, may be found in U. o patent specification No. 1 , 070 , 223 or in the complete specifications accompanying our co-pending applications Nos. 30, 97 /66 , 31+ , 978/66 and -+1 , 718/66 (Serial Nos !'120' 870' 1,122,323 and 1,138,540 As stated above, the quinoline derivatives of this invention possess valuable anti-coccidial properties. They are especially active against the intestinal species Eimeria brunetti, and certain of them are also active against thecaecal species E. tenella and E. necatrix. They are therefore useful as the active ingredient in veterinary compositions such as concentrated food pre-mixes or medieated foodstuffs to be used for the prophylactic treatment of coccidiosis in poultry or other domestic animals.
According to a further feature of the invention, therefore, we provide veterinary compositions comprising at least one of the quinoline derivatives of the invention - together with a non-toxic diluent or carrier.
The- veterinary compositions may "be, for example, concentrated food pre-mixes wherein the active ingredient is mixed with an inert diluent, for example kaolin, talc, calcium carbonate, fuller's earth, attapulgus clay or ground oyster shells, or is mixed with a foodstuff as diluent, for example whole ground corn, corn distillers dry grain, wheat shorts or corn cob meal. It is intended that the said pre-mixes should be further diluted with an animal foodstuff in order to provide a suitable medicated foodstuff which can be eaten directly by poultry or other domestic animals. It is preferred that such medicated foodstuff compositions intended for direct feeding to poultry should contain between aboiat 0. 0001 and about 0.1 by weight of active ingredient in the composition, and more particularly between 0.0005 and 0. 01% by weight in the food of the preferred active ingredients. It is likewise preferred that the concentrated pre-mixes should contain between about 0. 1% and about 25% by weight of "the active ingredient and more particularly between 0. 2% and 5% y weight of the preferred active ingredients.
The compositions of the invention may additionally contain one or more other compounds of known veterinary utility, for example one or more known coccidiostats , anthelmintics, or growth promotors, anti-bacterials or tranquilisers.
The invention is illustrated but not limited by the following Examples in which the parts are by weight^ and in Example 1 A mixture of 2+.2 parts of diethyl 3-benzyloxy- -n-propoxyanilinomethylenemalonate and 3 parts of phosphorus o^chioride is heated at 100°C. for 2.5 hours. The excess of phosphorus oxychloride is evaporated, and the residue poured onto ice. The resulting mixture is made alkaline with concentrated ammonium hydroxide, and the solid product is filtered off, washed with water, dried under vacuum, and crystallised from petroleum ether (b.p.60-80°C. ) . There is thus obtained ethyl 7-benzyloxy--+-chloro-6-n-propoxyquinoline-3-carboxylate , m. p.119-120°C. Example 2 mixture of 3· 7 parts of ethyl 7-benzyloxy-U-hydroxy-6-n-propoxy uinoline-3-carboxylate and 3*k parts of phosphorus oxychloride is shaken and heated at 100°C. for i hour, and is then poured onto ice. The resulting mixture is made alkaline with concentrated ammonium hydroxide, and the solid product is stirred and kept cold until it becomes entirely granular. The whole is then extracted with ether, and the extract dried and evaporated. The residue is crystallised from petroleum ether (b.p.60-80°C. ). There is thus obtained ethyl 7-benzyloxy--.-chloro-6-n-propoxyquinoline-3-carboxylate , m.p.119°C.
The above procedure is repeated except that the 3.7 parts of ethyl 7-benzyloxy----hydroxy-6-n-propoxy-quinoline-3-carboxylate are replaced by 3.1 parts of ethyl 7-benzyloxy- -hydroxyquinoline-3-carboxylate, 3*1 parts of ethyl 7-benzyloxy-6-n-butyl--+-hydroxyquinoline-3- carboxylate or 3.5 parts of methyl 7-benzyloxy-6-n-butyl- -hydroxyqulnoline-3rcar"boxylate, and there is thus obtained ethyl 7-benzyloxy- -c loroquinoline-3-carboxylate , m.p.l21°C. , ethyl 7-benzyloxy-6-n-butyl----chloroquinoline-3-carboxylate, m.p.90-92°C. , or methyl 7-benzyloxy-6-n-butyl- -chloroquinoline-3-carboxylate, m,p.85-86°C. respectively. Example 3 A mixture of 10 parts of ethyl 7-benzyloxy- -chloro-6-n-propoxyquinoline~3-carboxylate and a solution of 0.725 parts of sodium metal in 60 parts of dry ethanol is stirred and heated under reflux for 30 minutes. The ethanol is evaporated under reduced pressure, and the residue repeatedly extracted with hot ether. The ethereal solution is evaporated, and the residue is triturated with petroleum ether (b.p. 0-60°C. ). The resulting solid product is crystallised from petroleum ether (b.p.60-80°C. ) to give ethyl 7-benzyloxy----ethoxy-6-n-propoxyquinoline-3-carboxylate , m.p.60-6l°C.
The above procedure is repeated except that the 10 parts of ethyl 7-benzyloxy-l|.-chloro-6-n-propoxy-quinoline-3-carboxylate are replaced by 8.5 parts of ethyl 7-benzyloxy- -chloroq.uinoline-3-carboxylate. There is thus obtained ethyl 7-benzyloxy--+-ethoxyquinoline-3-carboxylate, m. .88°G.
Example k A mixture of 3.81 parts of ethyl 7-benzyloxy--+-hydroxy-6-n-propoxyquinoline-3-carboxylate, 2 parts of sodium acetate, and 88 parts of acetic anhydride is stirred and heated under reflux for 2¼ hours. The mixture is then filtered hot, and allowed to cool. The solid product is filtered off, washed with water, dried, and crystallised from absolute ethanol. There is thus . obtained ethyl lj.-acetoxy-7-benzyloxy-6-n-propoxyquinoline-3-carboxylate, m.pol60°C.
Example 5 The process described in Example 2 is repeated except that the 3· 7 parts of ethyl 7-benzyloxy- -hydroxy-6-n-propoxyquinoline-3-carboxylate are replaced by an equimolar amount of methyl 7-benzyloxy-l+-hydroxyquinoline-3-carboxylate, methyl 7-benzyloxy-ij.-hydroxy-6-n-propoxy-quinoline-3-carboxylate or ethyl 7-benzyloxy-6-allyloxy-U-hydroxyquinoline-3-carboxylate. There is thus obtained methyl 7-benzyloxy-i+-chloroquinoline-3-carboxylate, m.p.l20°C. (recrystallised from cyclohexane) , methyl 7-benzyloxy-6-n-propoxy- -chloroquinoline-3-carboxylate , m.p. l 6-lii.9°C. or ethyl 7-benzyloxy-6-allyloxy- -chloro-quinoline~3-carboxylate, m.p.173-17 °C. (recrystallised from a mixture of benzene and acetone) respectively.
Example 6 The process described in Example 3 is repeated except that the ethanol is replaced by methanol, and the ethy1 7-benzyloxy- -chloro-6-n-propoxyquinoline-3~ carboxylate is replaced by an equimolar amount of methyl 7-benzyloxy- -chloro-6-n-propoxyquinoline-3-carboxylate or methyl 7-benzyloxy-6-n-butyl- -chloroquinoline-3-carboxylate. There is thus obtained methyl 7-benzyloxy- 6-n-propoxy-l+-methoxyquinoline-3-carboxylate, m.p. ll6-117°C. [recrystallised from a mixture of "benzene and petroleum ether (b.p.60-80°C. ) ] , or methyl 7-benzyloxy-'6-n-butyl-i4.-methoxyquinoline-3-carboxylate, m.p.l05°C. [recrystallised from petroleum ether (b.p. l4-0-60°C. ) ] .
The above products are also obtained by ester exchange when the corresponding ethyl esters are used as starting materials, thus when the process described in Example 3 is repeated using n-butanol in place of ethanol there is obtained n-butyl 7-benzyloxy--4--n-butoxy-6-n-propoxyquinoline-3-carboxylate, m.p.53-55°C.
Example 7 The process decribed in Example k is repeated except that the 3·θ1 parts of ethyl 7-benzyloxy- -hydroxy' 6-n-propoxyquinoline-3-carboxylate are replaced by an equimolar amount of a -+-hydroxyqulnoline derivative of the formula:- OH and there is thus obtained a -.-acetoxy-quinoline derivative of the formula OoCO.CH The following i+-acetoxyquinoline derivatives may "be thus obtained: R1 E2 X k m.p. °C. Crystallisation Solvent Et "benzyl 0 methyl : 150 cyclo- hexane Et p_-chlorobenzyl 0 n-propyl 1-+8 cyclo- , hexane Me benzyl 0 n-butyl 123 methanol Et benzyl 0 n-octyl 88 ; cyclo- hexane Me n-dodecyl 0 n-butyl 75 Me benzyl 0 n-propyl li+0 Me n-octyl 0 n-butyl 71 By a strictly analogous procedure but replacing the acetic anhydride and sodium acetate by n-butyric anhydride and sodium butyrate, there is obtained ethyl 7-benzyloxy-6-n-propoxy- -n-butyryloxyquinoline-3-carboxylate, m.p.127-128°C. recrystallised from ethanol.
The preparation of the -hydroxyquinoline derivatives used as starting materials in the foregoing Examples 2, 1+, 5 and 7 is described in U.K. patent specification No. 1,070,223 and in our co-pending U.K. patent applications Nos. 30,97 /66, 3 , 978/66 and 1+1, 718/66 (Serial Nos. J-?9--¾T¾¾ . ΛΑ2.2ι ,323.^. Α3Α .5.4P.... ) , with the exception of the following: -ethyl 7-benzyloxy-6-n-octyloxy- -hydroxyquinoline-3-carboxylate, m.p.25ij.-2550C. , ethyl 7-dodecyloxy-6-n-propoxy- -hydroxyquinoline-3-carboxylate, m.p.2-+U-2i+60C. , ethyl 7- £-methoxybenzyloxy-6-n-propoxy--~hydroxyquinoline -3- carboxylate, m.p.255-256°C. , methyl 7- -fe-niethylthio- phenoxy)ethoxy-e-n-hutyl- -hydroxyquinoline^-carboxylate , m.p. 267°C., methyl 7-^-(£-nitrophenoxy)ethoxy-6-n-butyl--+- hydroxyquinoline-3-carboxylate, m.p.228°C, methyl 7-n- dodecyloxy-6-n-butyl- -hyo oxyquinoline-3-carboxylate, m.p.26-.°C. , and methyl 7-n-octyloxy-6-n-butyl-U-hydroxy- guinoline-3-carboxylate, m.p.267°C. -|_0 The above compounds are obtained by cyclisation of the condensation product of the appropriate aniline derivative with either dimethyl or diethyl methoxymethylene- malonate. The cyclisation may be carried out by the conventional procedures, i.e. either thermally or by using phosphorus oxychloride. The appropriate aniline derivatives may be obtained as follows : - 3-benzyloxy- -n-octylox aniline : 2-Benzyloxy- -nitrophenol is alkylated with n- octyl bromide in acetone in the presence of potassium carbonate to give 3-benzyloxy--+-n-octyloxynitrobenzene, m.p.57-58°C. , which is reduced to the above aniline derivative using sodium sulphide in ethanol. 3-n-dodecyloxy----n-propoxyaniline and 3-£-methoxybenzyloxy- i+-n-propoxyaniline : K 3-Hydroxy--+-n-propoxyacetanilide [Example 13 of D Serial No. 1, 120, 870 the specification of U.K. patent application No. 30 , 97 /66 ] is alkylated with either n-dodecyl bromide or _-methoxy- benzyl chloride in ethanol in the presence of potassium carbonate at 80°C. for 72 hours, and the resulting products are hydrolysed by being heated under reflux for 6 hours with potassium hydroxide in aqueous ethanol to give the. above aniline derivatives as oils. 3-β-(,-methylthiopheno )ethox --+-n-butylaniline and 3-β- (p.-nitrophenox ) ethoxy-U-n-butylaniline : -+-n-Butyl-3-P-bromoethoxyacetanilide is reacted with (methylthio)phenol or p_-nitrophenol in the presence of sodium ethoxide in ethanol using the general process described in Example 6 of U.Ko patent application No.
Serial No.1, 120, "870 , 97^/66/. The resulting products are hydrolysed with potassium hydroxide to give the above aniline derivatives as oils. 3-dodecyloxy- -n-butylaniline and 3-n-octyloxy- -n-butyl-aniline: -n-Butyl-3-hydroxyacetanilide is alkylated with either n-dodecyl bromide or n-octyl bromide in acetone in the presence of potassium carbonate at 60°C. for 72 hours. The resulting products are hydrolysed with potassium hydroxide in aqueous ethanol, and the corresponding aniline derivatives are obtained as oils.
Example 8 3 Parts of methyl 7-benzyloxy-6-n-propyl-i+.-acetoxyquinoline-3-carboxylate and 97 parts of whole ground corn are thoroughly mixed in a blending machine.
There is thus obtained a concentrated food pre-mix which may be mixed in suitable proportions with an animal foodstuff so that the medicated foodstuff so obtained can be fed to poultry for the prophylactic control of coccidiosis.
The whole ground corn in the above pre-mix may be replaced by corn distillers dry grain, wheat shorts, corn cob meal, fuller's earth, calcium carbonate, attapulgus clay or ground oyster shells.
The active ingredient in the above pre-mix may be replaced by any of the quinoline derivatives specifically described in this specification, but those quinoline derivatives which are indicated -as being preferred may be used to obtain the most useful concentrated pre-mixes.
Example 9 1 Part of a concentrated food pre-mix, obtained as described in Example 8, is uniformly dispersed in 2000 parts of commercial poultry starting mash. There is thus obtained a medicated foodstuff suitable for feeding to poultry for the prophylactic control of coccidiosis.

Claims (27)

1. 28530/ 2 ula: - wherein X stands for an oxygen atom, R stands for an alkyl radical, R stands for N-octyl or N-dodecyl radical, or ah aryloxyalkyl or aralkyl radical the aryl nucleus of either of which optionally bears one or more substituents selected from halogen atoms and alkyl, 3 alkoxy, alkylthio and nitro radicals, R stands for an alkoxy or ' . · , ' . · . ' 4 ' ■ acyloxy radical, and R stands for hydrogen or an alkyl, alkoxy or alkenyloxy radical;
2. Quinoline derivatives as claimed in claim 1, wherein X stands κ for an oxygen atom, R stands for an alkyl radical of 2 not more than 6 carbon atoms, R stands for an -octyl or N- dodecyl radical, or an aryloxyalkyl or aralkyl radical of not more than 15 carbon atoms the aryl nucleus of either of which optionally bears one or more substituents selected from chlorine and bromine atoms; nitro radicals, and alkyl, alkoxy and alkylthio of not more 3 than 6 carbon atoms, R stands for an alkoxy or alkanoyloxy radical 4 of not more than 6 carbon atoms, and R stands for hydrogen or an alkyl, alkoxy or alkenyloxy radical of not more than 10 carbon atoms.
3. Quinoline derivatives as claimed in clai 2, wherein 4 when X stands for an oxygen atom, R stands for an alkyl or alkoxy radical of not more than 10 carbon atoms in the 6 -position of the quinoline nucleus, or for an alkenyloxy radical of not more than 6 carbon atoms in the 6 -position of the quinoline nucleus. 28530/2 +
4. Quinoline derivatives as claimed in claim 1, wherein X stands for an oxygen atom, R1 stands for the methyl, ethyl, n- ■2 butyl radical, R stands for the n-octyl, n-dodecyl, 3-phenoxyethyl, W -phenoxyhexyl, benzyl, £-methoxybenzyl, ^-(p-methylphenoxy) ethyl, J3-(p-methylthiophenoxy)ethyl, J3-(j>-nitrophenoxy)ethyl or jo- 3 chlorobenzyl radical, R stands for a chlorine atom or the methoxy, ' 4 ethoxy, n-butoxy, acetoxy or n-butyryloxy radical, and R stands for the 6 -methyl, 6-n-propyl, 6-n-butyl, 6 -n-octyl- 6 -ethoxy, 6 -n- propoxy, 6 *isopropoxy, 6 -n-octyloxy, 6 -allyloxy or 6 -(2 -methyl - allyDoxy radical.
5. The qyinoline derivative: ethyl 7-benzyloxy-6 -n-propoxy- 4 - ac et oxyquinoline - 3 - c arboxylate.
6. The qyinoline derivatives: methyl 7-benzyloxy-6 -n-4- methoxyquinoline-3 -carboxylate, ethyl 7-benzyloxy-6 -isopropoxy-4- acetoxyquinoline-3-carboxylate, ethyl 7-benzyloxy-6 -ethoxy-4-acetoxy quinoline-3-carboxylate, ethyl 7 -n-dodecyl oxy-S -n-propoxy-4 -acetoxy- quinoline-3 -carboxylate, methyl 7-benzyloxy-6-allyloxy-4-acetoxy- qtiinoline-3 ^carboxylate, methyl 7-B-(jg-methylphenoxy)ethoxy-6 -η·«· butyl-4-acetoxyquinoline-3 -carboxylate, methyl 7-benzyloxy-6-n- propyl-4-acetoxyquinoline-3 -carboxylate, methyl 7-benzyloxy-6-n- butyl-4-acetoxyquinoline-3 -carboxylate, ethyl 7-jj-chlorobenzyloxy- 6 -n-propyl-4-acetoxyquinoline-3-carboxylate and ethyl 7-benzyloxy-? 6-n-propoxy-4-n-butyryloxyquinoline-3-carboxylate.
7. A process for the manufacture of those of the quinoline 3 derivatives claimed in claim 1 wherein R stands for an alkoxy 5 radical of the formula R 0-, which comprises the interaction of a 28530/2 wherein R # R , R and X h ye the meanings stated in claim 1, 5 -and Z stands for a halogen atom, with a salt of the formula R O A '5 ψ wherein R stands for an alkyl radical and A stands for a metal ion; ·'· ' 0
8. , A process as claimed in claim 7 wherein R stands for an alkyl radical of not more than 6 carbon atoms, for example the m ethyl j ethyl or n -butyl radical.
9. A process as claimed in claim 7 or 8 wherein A stands for an ion derived from an alkali metal, for example the sodium or potassiu ion.
10. A process for the manufacture of those of the quinoline 3 derivatives claimed in claim 1 wherein R stands for an acyloxy radical, which comprises the interaction of a hydroxyquinoline derivative of the formula: - wherein R , R , R and X have the meanings stated in claim 1, sdawith an acylating agent .
11. ; A process as claimed in claim 10 wherein the acylat- 6 ing agent is derived from an acid of the formula R . COOH, wherein 6 28530/ 2 4».
12. A process as claimed in claim 10 or 11 wherein the acylating agent is an acid anhydride.
13. Veterinary compositions comprising at least one of the quinoline derivatives claimed in claim 1 together with a nontoxic diluent or carrier.
14. Compositions as claimed in claim 13 which are in the form of concentrated food pre -mixes wherein the active ingredient is mixed with an inert diluent or a foodstuff as diluent.
15. Compositions as claimed in claim 14 wherein the insert' diluent is kaolin, talc, calcium carbonate, fuller's earth, attapulgus clay or ground oyster sheels.
16. Compositions as claimed in claim 14 wherein the foodstuff is whole ground corn, corn distillers dry grain, wheat shorts or corn cob meal.
17. Composition's as claimed in any of claims 14 to 16 which contain between 0. 1% and 25% by weight of the active ingredient.
18. Compositions as claimed in claim 13 which are medicated foodstuff compositions containing between 0. 0001% and 0. 1% by weight of active ingredient.
19. Compositions as claimed in claim 13 which additionally contain one or more known occidiostats, anthelmintics, growth promoters, antibacterials or tranquilisers.
20. , A method for the prophylactic treatment of coccidiosis in poultry or other domestic animals which comprises feeding to such poultry or other domestic animals a. medicated foodstuff as claimed in claim 18. 28530/2 *
21. A quinoline derivative as claimed in claim 1 substantially as described in any of Examples 1 to 4.
22. A quinoline derivative as claimed in claim 1 substantially as described in any of Examples 5 to 7.
23. A process as claimed in claim 7 substantially as described in Example 1.
24. A process as claimed in claim 9 substantially as described in Example 2 or 5.
25. A process as claimed in claim 7 substantially as described in Example 3 or 6.
26. A process as claimed in claim 10 substantially as described in Example 4 or 7,
27. A veterinary composition as claimed in claim 13 substantially as described in Example 8 or 9. ■ S. HOROWITZ & CO. AGENTS FOR APPLICANTS
IL2853067A 1966-09-15 1967-08-20 Quinoline-3-carboxylic acid ester derivatives IL28530A (en)

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IL2853067A IL28530A (en) 1966-09-15 1967-08-20 Quinoline-3-carboxylic acid ester derivatives

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BE (1) BE703887A (en)
CH (1) CH500193A (en)
DE (1) DE1695286A1 (en)
FR (1) FR1573838A (en)
GB (1) GB1138539A (en)
IL (1) IL28530A (en)
NL (1) NL6711776A (en)
SE (1) SE333142B (en)

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Publication number Priority date Publication date Assignee Title
DE2103805C3 (en) * 1970-01-28 1980-03-20 Sumitomo Chemical Co., Ltd., Osaka (Japan) Process for the preparation of N-substituted 6,7-methylenedioxy-4-quinolones
WO2016125187A1 (en) * 2015-02-03 2016-08-11 Council Of Scientific & Industrial Research Novel quinoline derivatives and preparation thereof

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BE703887A (en) 1968-03-14
GB1138539A (en) 1969-01-01
FR1573838A (en) 1969-07-11
SE333142B (en) 1971-03-08
NL6711776A (en) 1968-03-18
CH500193A (en) 1970-12-15
DE1695286A1 (en) 1971-03-18

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