CS242022B1 - Substituted anilides of 3-benzyl-5-chlorosalicylic acid - Google Patents
Substituted anilides of 3-benzyl-5-chlorosalicylic acid Download PDFInfo
- Publication number
- CS242022B1 CS242022B1 CS847794A CS779484A CS242022B1 CS 242022 B1 CS242022 B1 CS 242022B1 CS 847794 A CS847794 A CS 847794A CS 779484 A CS779484 A CS 779484A CS 242022 B1 CS242022 B1 CS 242022B1
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- benzyl
- chlorosalicylic acid
- nitroaniline
- formula
- substituted
- Prior art date
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- 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 title abstract description 6
- 229940051881 anilide analgesics and antipyretics Drugs 0.000 title abstract 2
- 150000003931 anilides Chemical class 0.000 title 1
- 239000000460 chlorine Substances 0.000 claims abstract description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 4
- 239000001257 hydrogen Substances 0.000 claims abstract description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 4
- RORHDOKDOHXHKF-UHFFFAOYSA-N OC(C(C(NC1=CC=CC=C1)=O)=C1)=C(CC2=CC=CC=C2)C=C1Cl Chemical class OC(C(C(NC1=CC=CC=C1)=O)=C1)=C(CC2=CC=CC=C2)C=C1Cl RORHDOKDOHXHKF-UHFFFAOYSA-N 0.000 claims description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 abstract description 6
- 239000008096 xylene Substances 0.000 abstract description 6
- 241001464384 Hymenolepis nana Species 0.000 abstract description 5
- 230000000507 anthelmentic effect Effects 0.000 abstract description 5
- LOCWBQIWHWIRGN-UHFFFAOYSA-N 2-chloro-4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1Cl LOCWBQIWHWIRGN-UHFFFAOYSA-N 0.000 abstract description 4
- TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 abstract description 4
- 108010034145 Helminth Proteins Proteins 0.000 abstract description 4
- 244000000013 helminth Species 0.000 abstract description 4
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 description 5
- 238000009835 boiling Methods 0.000 description 4
- 230000009545 invasion Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- -1 3-benzyl-5-chlorosalicyl Chemical group 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- CAQWNKXTMBFBGI-UHFFFAOYSA-N C.[Na] Chemical compound C.[Na] CAQWNKXTMBFBGI-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- RJMUSRYZPJIFPJ-UHFFFAOYSA-N niclosamide Chemical compound OC1=CC=C(Cl)C=C1C(=O)NC1=CC=C([N+]([O-])=O)C=C1Cl RJMUSRYZPJIFPJ-UHFFFAOYSA-N 0.000 description 1
- 229960001920 niclosamide Drugs 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000001424 substituent group Chemical group 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
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
Substituované anilidy kyseliny 3-benzyl- -5-chlorsalicylové obecného vzorce I kde R* 1 Je atom vodíku nebo atom chloru, R2 je nitroskupina. Tyto nové, dosud nepopsané látky vykazují anthelmintickou účinnost vůči helmintu Hymenolepis nana. Lze je snadno připravit reakcí kyseliny 3-benzyl-5-chlorsalicylové s 4-nitroanilinem nebo 2-chlor-4-nitroanilinem v xylenu za přítomnosti íosfortrichloridu za zvýšené teplotySubstituted 3-benzyl- anilides -5-chlorosalicyl of formula I where R * 1 is hydrogen or chlorine, R2 is nitro. These new, not yet described substances show anthelmintic activity against the helminth Hymenolepis nana. They can be easily prepared by reaction of 3-benzyl-5-chlorosalicylic acid with 4-nitroaniline or 2-chloro-4-nitroaniline in xylene in the presence of phosphorus chloride at elevated temperature
Description
Substituované anilidy kyseliny 3-benzyl-5-chlorsalicylové obecného vzorce ISubstituted 3-benzyl-5-chlorosalicylic acid anilides of formula I
kde R* 1 Je atom vodíku nebo atom chloru, R2 je nitroskupina.wherein R * 1 is hydrogen or chlorine, R 2 is nitro.
Tyto nové, dosud nepopsané látky vykazují anthelmintickou účinnost vůči helmintu Hymenolepis nana. Lze je snadno připravit reakcí kyseliny 3-benzyl-5-chlorsalicylové s 4-nitroanilinem nebo 2-chlor-4-nitroanilinem v xylenu za přítomnosti íosfortrichloridu za zvýšené teploty.These novel, yet undescribed substances exhibit anthelmintic activity against Hymenolepis nana helminth. They can be readily prepared by reacting 3-benzyl-5-chlorosalicylic acid with 4-nitroaniline or 2-chloro-4-nitroaniline in xylene in the presence of phosphoric chloride at elevated temperature.
Vynález se týká substituovaných anilidů kyseliny 3-benzyl-5-chlorsalicylové obecného' vzorce IThe present invention relates to substituted 3-benzyl-5-chlorosalicylic acid anilides of formula (I)
kde R1 značí atom vodíku nebo atom chloru, R2 je nitroskupina.wherein R 1 is hydrogen or chlorine, R 2 is nitro.
Tyto nové dosud nepopsané látky vykazují použitelnou anthelmintickou účinnost, zejména proti modelovému helmintu Hymenolepis nana.These novel substances, which have not yet been described, exhibit useful anthelmintic activity, in particular against the model helminth of Hymenolepis nana.
Sloučeniny obecného vzorce I lze podle vynálezu připravit reakcí o sobě známé kyseliny 3-benzyl-5-chlorsalicylové (Čs. AO č. 177 663) s 4-nitr oanilinem nebo 2-chlor-4-nitroanilinem v přítomnosti fosfortrichloridu v prostředí inertního rozpouštědla za zvýšené teploty, výhodně s 0,4 molu fosfortrichlořidu v xylenu při teplotě 130 až 140 stupňů Celsia.The compounds of the 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-nitroaniline or 2-chloro-4-nitroaniline in the presence of phosphorotrichloride in an inert solvent. elevated temperatures, preferably with 0.4 moles of phosfortrichloride in xylene at a temperature of 130 to 140 degrees Celsius.
Hodnocení anthelmintické účinnosti proti modelovému helmintu Hymenolepis nanaEvaluation of anthelmintic efficacy against model helminth Hymenolepis nana
Testy byly provedeny na myších samcích kmene H s hmotností 10 až 13 g ve skupinách po 6 kusech. Dvě ze tří kontrolních skupin byly invadované, neléčené, třetí byla invadoivaná, léčená standardním přípravkem — piperazinovou solí niclosamidu — vůči němuž byla účinnost látek porovnávána.The tests were performed on male H strain mice weighing 10-13 g in groups of 6 each. Two of the three control groups were invaded, untreated, the third was invadivated, treated with a standard formulation - niclosamide piperazine salt - against which the efficacy of the compounds was compared.
Invaze byla prováděna sondou perorálně vždy 300 zralými vajíčky Hymenolepis nana v objemu 0,25 ml/myš.Invasion was performed by probing orally with 300 mature Hymenolepis nana eggs in a volume of 0.25 ml / mouse.
Sloučeniny obecného vzorce I byly aplikovány 13. a 14. den po invazi perorálně sondou v dávce 150 mg/kg ž. hm. Standard byl aplikován rovněž 13. a 14. den po invazi v dávce 150 mg/kg ž. hm., což přepočteno na niclosamid znamená dávku 4,58 . . 10 mol/kg ž. hm.Compounds of formula I were administered orally by gavage at 150 mg / kg body weight on days 13 and 14 after invasion. hm. The standard was also applied on days 13 and 14 after invasion at 150 mg / kg b.w. %, which, calculated as niclosamide, represents a dose of 4.58. . 10 mol / kg bw hm.
Anthelmintická účinnost sloučenin obecného vzorce I vyjádřená v procentech metodou nepřímé aktivity podle Stewarda je uvedena níže.The anthelmintic activity of the compounds of formula I, expressed as a percentage by the Steward indirect activity method, is given below.
Substituenty ve vzorci I dávka mol/kg ž. R1 R2 The substituents in formula I dose mol / kg bw. R 1 R 2
H NOz 3,9 . ΙΟ4 H NO2 3.9. ΙΟ 4
Cl NO2 3,6 . 10~4 Cl NO2 3.6. 10 ~ 4
Způsob přípravy látek podle 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.
PřikladlHe did
4-Nitroanilid kyseliny4-Nitroanilide acid
-3-benzyl-5-chlorsalicylové-3-benzyl-5-chlorosalicyl
Směs 26,2 g kyseliny 3-benzyl-5-chlorsalicylové (0,1 mol) a 13,8 g 4-nitroanilinu (0,1 mol) a 500 ml xylenu byla zahřáta k varu a k vroucímu roztoku prikapáno 5,5 g fosfortrichloridu (0,04 mol). Reakční směs byla zahřívána při teplotě 130 až 140 °C po dobu 8 h pod zpětným chladičem a pak ještě za horka oddělena od nerozpuštěného anorganického zbytku. Ochlazením vykrystalovaná látka byla odsáta a promyta xylenem, 5% vodným roztokem hydrogenuhličihm. účinnost v % příklad provedení metodou nepřímé aktivityA mixture of 26.2 g of 3-benzyl-5-chlorosalicylic acid (0.1 mol) and 13.8 g of 4-nitroaniline (0.1 mol) and 500 ml of xylene was heated to boiling and 5.5 g of fosfortrichloride were added dropwise to the boiling solution. (0.04 mol). The reaction mixture was heated at 130 to 140 ° C for 8 h under reflux and then separated from the undissolved inorganic residue while still hot. The crystallized solid was filtered off with suction and washed with xylene, 5% aqueous bicarbonate. efficiency in% Example of indirect activity method
80,9 180.9 1
62,0 2 tanu sodného a vodou. Překrystalováním surové látky z acetonu bylo získáno 35,51 g (92,8 o/o) látky o t. t. 191 °C.62.0 2 sodium methane and water. Recrystallization of the crude material from acetone gave 35.51 g (92.8% w / w) of m.p. 191 ° C.
Příklad 2Example 2
2-Chlor-4-nitroanilid kyseliny2-Chloro-4-nitroanilide acid
3-benzyl-5-chlorsalicylové3-benzyl-5-chlorosalicyl
Směs 17,3 g kyseliny 3-benzyl-5-chlorsalicylové (66 mmol) a 11,4 g 2-chlor-4-nitroanilinu (66 mmol) a 140 ml xylenu byla zahřáta k varu a k vroucímu roztoku přikapáno 3,15 g fosfortrichloridu (23 mmol). Reakční směs byla zahřívána pří teplotě 130 až 140 °C po dobu 7 h pod zpětným chladičem a pak po ochlazení byla vytřepána 5% vodným roztokem hydrogenuhličitanu sodného. Organická vrstva byla destilací za tlaku 1,3 kPa zbavena organického rozpouštědla a odparek překrystalován ze směsi chloroformu s petroletherem. Bylo získánoA mixture of 17.3 g of 3-benzyl-5-chlorosalicylic acid (66 mmol) and 11.4 g of 2-chloro-4-nitroaniline (66 mmol) and 140 ml of xylene was heated to boiling and 3.15 g of fosfortrichloride added dropwise to the boiling solution. (23 mmol). The reaction mixture was heated at 130-140 ° C for 7 h under reflux and then, after cooling, shaken with 5% aqueous sodium bicarbonate. The organic layer was freed from the organic solvent by distillation at 50 mbar and the residue was recrystallized from chloroform-petroleum ether. It was obtained
24,9 g (90%) látky o t. t. 129 až 130 °C.24.9 g (90%), mp 129-130 ° C.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS847794A CS242022B1 (en) | 1984-10-12 | 1984-10-12 | Substituted anilides of 3-benzyl-5-chlorosalicylic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS847794A CS242022B1 (en) | 1984-10-12 | 1984-10-12 | Substituted anilides of 3-benzyl-5-chlorosalicylic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS779484A1 CS779484A1 (en) | 1985-08-15 |
| CS242022B1 true CS242022B1 (en) | 1986-04-17 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS847794A CS242022B1 (en) | 1984-10-12 | 1984-10-12 | Substituted anilides of 3-benzyl-5-chlorosalicylic acid |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS242022B1 (en) |
-
1984
- 1984-10-12 CS CS847794A patent/CS242022B1/en unknown
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| Publication number | Publication date |
|---|---|
| CS779484A1 (en) | 1985-08-15 |
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