CS242024B1 - Substituted anilides of 3-benzyl-5-halogensalicylic acid - Google Patents
Substituted anilides of 3-benzyl-5-halogensalicylic acid Download PDFInfo
- Publication number
- CS242024B1 CS242024B1 CS847797A CS779784A CS242024B1 CS 242024 B1 CS242024 B1 CS 242024B1 CS 847797 A CS847797 A CS 847797A CS 779784 A CS779784 A CS 779784A CS 242024 B1 CS242024 B1 CS 242024B1
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- benzyl
- acid
- halogensalicylic
- substituted anilides
- chlorine
- Prior art date
Links
- 229940051881 anilide analgesics and antipyretics Drugs 0.000 title claims description 3
- 150000003931 anilides Chemical class 0.000 title claims description 3
- 239000002253 acid Substances 0.000 title description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 description 6
- 241000760148 Aspiculuris tetraptera Species 0.000 description 5
- 108010034145 Helminth Proteins Proteins 0.000 description 5
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 5
- 244000000013 helminth Species 0.000 description 5
- 239000008096 xylene Substances 0.000 description 5
- -1 3-Benzyl-5-chlorosalicylic acid 4-bromanilide Chemical compound 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 230000000507 anthelmentic effect Effects 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- NATVSFWWYVJTAZ-UHFFFAOYSA-N 2,4,6-trichloroaniline Chemical compound NC1=C(Cl)C=C(Cl)C=C1Cl NATVSFWWYVJTAZ-UHFFFAOYSA-N 0.000 description 3
- WYMIFSBIOKNUSJ-UHFFFAOYSA-N 3-benzyl-5-bromo-2-hydroxybenzoic acid Chemical compound OC(=O)C1=CC(Br)=CC(CC=2C=CC=CC=2)=C1O WYMIFSBIOKNUSJ-UHFFFAOYSA-N 0.000 description 3
- ZFPZIPXGQJRDLB-UHFFFAOYSA-N 3-benzyl-5-chloro-2-hydroxybenzoic acid Chemical compound OC(=O)C1=CC(Cl)=CC(CC=2C=CC=CC=2)=C1O ZFPZIPXGQJRDLB-UHFFFAOYSA-N 0.000 description 3
- WDFQBORIUYODSI-UHFFFAOYSA-N 4-bromoaniline Chemical compound NC1=CC=C(Br)C=C1 WDFQBORIUYODSI-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 238000005275 alloying Methods 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Description
22
Substituované anilidy kyseliny 3-benzyl-5-halogensalicylové obecného vzorce ISubstituted 3-benzyl-5-haloalicylic acid anilides of formula I
kde X je atom chloru, R1 a R3 je atom vodíku a R2 je atom bromu, nebo X je atom bromu, R1, R2 a R3 je atom chloru. Způsob jejich výroby spočívá v reakci kyseliny 3-benzyl-5-chlorsalicylové s 4-bromanilinem, nebo v reakci kyseliny 3-benzyl-5-bromsalicylové s 2,4,6-trichloranilinem v xylenu za přítomnosti fosfortrichloridu za zvýšené teploty.wherein X is chlorine, R 1 and R 3 is hydrogen and R 2 is a bromine atom, or X is bromine, R @ 1, R @ 2 and R @ 3 is chlorine. A process for their preparation consists in reacting 3-benzyl-5-chlorosalicylic acid with 4-bromoaniline, or reacting 3-benzyl-5-bromosalicylic acid with 2,4,6-trichloraniline in xylene in the presence of phosphorotrichloride at elevated temperature.
Tyto nové, dosud nepopsané, látky vykazují anthelmintickou účinnost proti modelovému helmintu Aspiculuris tetraptera.These new, not yet described, compounds exhibit anthelmintic activity against the Aspiculuris tetraptera model helminth.
Vynález se týká substituovaných anilifl^ kyseliny 3-benzyl-5-halqgjfensillicylové Obecného vzorce IThe present invention relates to substituted 3-benzyl-5-halogeno-phenyl-sillicylic acid aniliphenylsulfonic acids of formula I
(I) kde X je atom chloru, R1 a R3 je atom vodíku a R2 je atom bromu, nebo X je atom bromu, R1, R2 a R3 je atom chloru.(I) wherein X is chlorine, R 1 and R 3 is hydrogen and R 2 is a bromine atom, or X is bromine, R @ 1, R @ 2 and R @ 3 is chlorine.
Tyto nové dosud nepopsané sloučeniny vykazují použitelnou anthelmintickou účinnost, zejména proti modelovému helmintu Aspiculuris tetraptera.These novel compounds, which have not been described yet, exhibit useful anthelmintic activity, particularly against the Aspiculuris tetraptera model helminth.
Sloučeniny obecného vzorce I lze podle vynálezu připravit reakcí o sobě známé kyseliny 3-benzyl-5-chlorsalicylové (Čs. AO č. 177 663) s 4-bromanilinem, nebo· reakcí o sobě známé kyseliny 3-benzyl-5-bromsalicylové (Čs. AO č. 177 663) s 2,4,6-trichloranilinem, v přítomnosti fosfortrichloridu v prostředí Inertního rozpouštědla za zvýšené teploty, výhodně s 0,35 molárním množstvím fosfortrichloridu v xylenu při teplotě 130 až 140 °C.The compounds of formula (I) according to the invention can be prepared by reacting the known 3-benzyl-5-chlorosalicylic acid (No. AO No. 177 663) with 4-bromoaniline, or by reacting the known 3-benzyl-5-bromosalicylic acid AO No. 177,663) with 2,4,6-trichloroaniline, in the presence of fosfortrichloride in an inert solvent medium at elevated temperature, preferably with a 0.35 molar amount of phosphfortrichloride in xylene at 130-140 ° C.
Hodnocení anthelmintické účinnosti proti modelovému helmintu Aspiculuris tetrapteraEvaluation of anthelmintic efficacy against Aspiculuris tetraptera model helminth
Zkoušky byly provedeny na myších samcích kmene SPF/Velaz s hmotností 18 až 20 gramů ve skupinách po 3 kusech. Myši byly invadovány způsobem per os dávkou 80 až 100 vajíček/myš modelového helmintu Aspiculuris tetraptera a po ukončení vývinu parazita do pohlavní zralosti byly aplikovány látky obecného vzorce I. Látky byly aplikovány per os duodenální sondou v Dorfmanově činidle v dávce 150 mg/kg a 75 mg/kg po dobu 3 dní. Po 7 dnech od prvé aplikace byl makroskopicky u dekapitovaných myší zjištěn počet červů ve střevě v porovnání s kontrolní skupinou neléčených zvířat a výpočtem podle Stewarda stanovena anthelmintická účinnost.The tests were performed on male SPF / Velaz mice weighing 18-20 grams in groups of 3 pieces each. Mice were invaded orally at 80-100 eggs / mouse of Aspiculuris tetraptera model helminth, and after parasite development to sexual maturity, compounds of Formula I were administered orally. The compounds were administered orally by duodenal gavage in Dorfman's reagent at 150 mg / kg and 75 mg. mg / kg for 3 days. 7 days after the first administration, the number of worms in the intestine was determined macroscopically in the decapitated mice as compared to the control group of untreated animals and the anthelmintic efficacy was determined by the Steward calculation.
U 4-bromanilidu kyseliny 3-benzyl-5-chlorsalicylové byla zjištěna 96% účinnost, u 2,4,6-trichloranilidu kyseliny 3-benzyl-5-bromsalicylové 85% účinnost proti helmintu Aspiculuris tetraptera.3-Benzyl-5-chlorosalicylic acid 4-bromanilide showed 96% activity, 3-benzyl-5-bromosalicylic acid 2,4,6-trichloranilide 85% activity against Aspiculuris tetraptera helminth.
Způsob přípravy látek uvedených ve vynálezu je jednoduchý a poskytuje žádané produkty v uspokojivých výtěžcích. Bližší podrobnosti vyplývají z následujících příkladů provedení. Uvedené příklady vynález pouze ilustrují, nikoliv omezují.The process for preparing the compounds of the invention is simple and provides the desired products in satisfactory yields. Further details are given in the following examples. The examples given are merely illustrative and not limiting.
Příklad 1Example 1
4-Bromanilid kyseliny4-Bromanilide acid
3-benzyl-5-chlorsalicylové3-benzyl-5-chlorosalicyl
Směs 8,68 g kyseliny 3-benzyl-5-chlorsalicylové (33 mmolj a 5,7 g 4-bromanilinu (33 mrnol) a 70 ml xylenu byla zahřáta k varu a k vroucímu roztoku bylo přikapáno· 1,58 fosfortrichloridu (11,5 mmol) Reakční směs byla zahřívána při teplotě 130 až 140 °C po dobu 4 h pod zpětným chladičem a pak po ochlazení byla vytřepána 5% vodným roztokem hydrOgenuhllčitanu sodného. Organická vrstva byla destilací za tlaku 1,3 kPa zbavena rozpouštědla a odparek překrystalován ze směsi chloroformu s petroletherem. Bylo získáno 12,68 g (92,5%) látky o t. t. 135 °C.A mixture of 8.68 g of 3-benzyl-5-chlorosalicylic acid (33 mmol) and 5.7 g of 4-bromoaniline (33 moles) and 70 ml of xylene was heated to boiling and 1.58 phosphoricrichloride (11.5 ml) was added dropwise to the boiling solution. mmol) The reaction mixture was heated at 130-140 ° C for 4 h under reflux and then, after cooling, was shaken out with 5% aqueous sodium bicarbonate solution, the organic layer was freed from the solvent by distillation at 50 mbar and the residue was recrystallized from the mixture. of chloroform with petroleum ether, 12.68 g (92.5%) of m.p. 135 ° C.
Příklad 2Example 2
2,4,6-Trichloranilid kyselinyAcid 2,4,6-trichloroanilide
3-benzyl-5-bromsalicylové3-benzyl-5-bromosalicyl
Směs 10,13 g kyseliny 3-benzyl-5-bromsalicylové (33 mmol) a 6,49 g 2,4,6-trichloranilinu (33 mmol) a 70 ml xylenu byla zahřáta k varu a k vroucímu roztoku bylo přikapáno 1,58 gramu fosfortrichloridu (11,5 mmol). Reakční směs byla zahřívána při teplotě 130 až 140 °C po dobu 6 h pod zpětným chladičem. Pak ještě za horka oddělena slitím od nerozpuštěného anorganického zbytku. Látka vykrystalovaná po ochlazení byla po odsátí promyta xylenem, 5% vodným roztokem hydrogenuhličitanu sodného a vodou. Krystalizací z chloroformu bylo získáno 14,25 g (89%) látky o t. t.A mixture of 10.13 g of 3-benzyl-5-bromosalicylic acid (33 mmol) and 6.49 g of 2,4,6-trichloroaniline (33 mmol) and 70 ml of xylene was heated to boiling and 1.58 g was added dropwise to the boiling solution. phosphoric acid (11.5 mmol). The reaction mixture was heated at 130-140 ° C for 6 h under reflux. Then, while still hot, separated by alloying from the undissolved inorganic residue. The material crystallized upon cooling was washed with xylene, 5% aqueous sodium bicarbonate solution and water after aspiration. Crystallization from chloroform gave 14.25 g (89%) of m.p.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS847797A CS242024B1 (en) | 1984-10-12 | 1984-10-12 | Substituted anilides of 3-benzyl-5-halogensalicylic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS847797A CS242024B1 (en) | 1984-10-12 | 1984-10-12 | Substituted anilides of 3-benzyl-5-halogensalicylic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS779784A1 CS779784A1 (en) | 1985-08-15 |
| CS242024B1 true CS242024B1 (en) | 1986-04-17 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS847797A CS242024B1 (en) | 1984-10-12 | 1984-10-12 | Substituted anilides of 3-benzyl-5-halogensalicylic acid |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS242024B1 (en) |
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1984
- 1984-10-12 CS CS847797A patent/CS242024B1/en unknown
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| Publication number | Publication date |
|---|---|
| CS779784A1 (en) | 1985-08-15 |
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