US3075975A - Anthelmintic distilbazoles and method - Google Patents

Anthelmintic distilbazoles and method Download PDF

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US3075975A
US3075975A US115996A US11599661A US3075975A US 3075975 A US3075975 A US 3075975A US 115996 A US115996 A US 115996A US 11599661 A US11599661 A US 11599661A US 3075975 A US3075975 A US 3075975A
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lutidine
bis
anthelmintic
distilbazoles
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US115996A
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Arthur P Phillips
Robert B Burrows
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SmithKline Beecham Corp
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Burroughs Wellcome Co USA
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Priority to NL277327D priority Critical patent/NL277327A/xx
Priority claimed from US104798A external-priority patent/US3085935A/en
Application filed by Burroughs Wellcome Co USA filed Critical Burroughs Wellcome Co USA
Priority to US115996A priority patent/US3075975A/en
Priority to GB22626/61A priority patent/GB1009301A/en
Priority to DE19621470413 priority patent/DE1470413A1/en
Priority to DK179562AA priority patent/DK104234C/en
Priority to CH480662A priority patent/CH413836A/en
Priority to ES276612A priority patent/ES276612A1/en
Priority to LU41596D priority patent/LU41596A1/xx
Priority to BR138334/62A priority patent/BR6238334D0/en
Priority to FR895385A priority patent/FR1320520A/en
Priority to FR895386A priority patent/FR1841M/en
Publication of US3075975A publication Critical patent/US3075975A/en
Application granted granted Critical
Priority to OA52810A priority patent/OA02352A/en
Priority to MY196793A priority patent/MY6700093A/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
    • C07D213/16—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine ring
    • C07D213/20—Quaternary compounds thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/36—Radicals substituted by singly-bound nitrogen atoms
    • C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B23/00—Methine or polymethine dyes, e.g. cyanine dyes
    • C09B23/14—Styryl dyes

Definitions

  • This parasite (Eêtrobius vermicularz's) is the most common nematode parasite of the human inhabitants of North America and Europe. It is particularly common among young children and frequently spreads through a family. Since it dwells in the lower intestine, it is difficult to eradicate. At the same time, while it is a nuisance and shocking to the sensibilities of many people, it is not usually dangerous and serious effects upon the host have not been clearly demonstrated.
  • the invention comprises a novel group of distilbazole compounds of the preceding formula and the administration of these compounds in the treatment of nematode infestations, particulary human pin-worms.
  • Table I are shown the result of tests with illustrative compounds of this invention and of three close relatives, first in regard to toxicity (LD in mice and secondly in eliminating the pin-worm of mice, Syphacia obvelata. (This parasite has been found in past experience to be of particular value as vectors which indicate drugs useful against the human pin-worm.) It will be seen that the first three compounds of the table, having dimethylamino or diethylamino groups on the benzene rings have LD values of 2535 mg./kg. while high efficiency against pinworms requires /3 to /2 of that amount.
  • the six following compounds are active at about the same level, but have an entirely different order of toxicity (LD being over 1000 mg./kg. in four of the six cases). All of these compounds were administered as iodides wherefore differences in molecular weights were negligible as regards relative toxicity.
  • n o om solvents the usual metathetical conversions of anions (e.g. that of an iodide to a chloride by treatment with silver chloride) are rather unsatisfactory. It is consequently convenient to have as the anion of the lutidine quaternary salt that anion which is desired in the product. Again, conveniently, the anion may be that introduced by the alkyiating agent.
  • the anion may be that introduced by the alkyiating agent.
  • alkylation of 2,6-lutidine with propyl p-toluenesulfonate aflfords 2,6- dimethyl-l-propylpyridiniurn tosylate which is then condensed with p-pyrrolidinobenzaldehyde or p-piperidinobenzaldehyde to give 2,6-bis-p-pyrrolidino or piperidino styrylpyridine n-propyl tosylate.
  • metathetical interconversions are readily accomplished at this stage so that to make a Compound II where X is chloride, it is easy to convert 2,6- lutidine methiodide to the metho-chloride by warming with methanolic hydrogen chloride.
  • the compounds '11 are dark-colored crystals whose surface color ranges from dark red to almost black.
  • EXAMPLE 1 Preparations .dissolved in 200 cc. of methanol and hydrogen chloride gas was run in until 20 g. had been absorbed. The solution was then warmed on the steam bath, most of the solvent being gradually distilled out. One hundred cc. of 10% methanolic hydrogen chloride was then added and the process repeated. Finally the flask was evacurated on the steam bath. The rather hydroscopic residue was the etho-chloride of 2,6-lutidine and was suitable for synthetic purposes without further manipulation.
  • N-phenylpyrr'oIidine A mixture of 216 g. of 1,4-dibromobutane, 500 cc. of methanol and 465 g. of aniline was refluxed for 5 hours at 100 C. Methanol was evaporated and 120 g. of sodium hydroxide (as 40-50% aqueous solution) was added to the residue. The organic layer was taken up in ether and dried over anhydrous 4, potassium carbonate. After removing potassium carbonate and ether the excess aniline was distilled in vacuo and saved, and the product was collected. N-phenylpyrrolidine boiled at 133-134 C. at 19 mm.; the yield was 130 g. (88-90%).
  • mice Single Percent Mice dose worms cleared] mgjkg. removed Mice dosed 48-236 (CHmN H1 25 20 100 /5 1.5 100 5/5 97 7/13 5 92 2/13 2.5 51 0/6 61-2 (CHmN ch 35 100 3/3 10 97 5/9 7.5 92 1/6 5 86 2/6 2.5 69 1/6 60-434 (C1H3)2N- CH3 20 99 4/5 10 99 4/5 5 67 1/12 61-31 N CH3 1 000 20 96 3/6 10 92 2 6 5 so 2/6 61-32 N Cm: 1,350 2g 13g a 6 2/3 61-75 N CHZCHZCHS.
  • R X- wherein n has the values of 2 and 3, R is selected from 2,534,237 Cusic Dec. 19, 1950 the class consisting of the methyl, ethyl and n-propyl 2,890,982 Natt June 16, 1959 groups, and X- is an anion derived from a pharmaceutically acceptable acid.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Pyridine Compounds (AREA)

Description

United States Patent 3 075,975 ANTHELMINTI'C BISIILBAZQLES AND METHOD Arthur P. Phillips, Tuckahoe, and Robert B. Burrows, Ardsley, N.Y., assignors to Burroughs Wellcome & C0. (U.S.A.) Ina, Tuclrahoe, N.Y., a corporation of New York No Drawing. Filed June 7, 1961, Ser. No. 115,996 7 Claims. (Cl. 260-2409) This application relates to a novel group of distilbazole derivatives having anthelmintic activity, especially against human pin-worms. This is a continuation-in-part of our ccpending application Serial No. 104,798, filed April 24, 1961.
This parasite (Erzterobius vermicularz's) is the most common nematode parasite of the human inhabitants of North America and Europe. It is particularly common among young children and frequently spreads through a family. Since it dwells in the lower intestine, it is difficult to eradicate. At the same time, while it is a nuisance and shocking to the sensibilities of many people, it is not usually dangerous and serious effects upon the host have not been clearly demonstrated.
Because of the relatively innocuous nature of this para site, clinicians rightly insist that any remedy should it self be non-toxic and otherwise harmless (whereas with more serious infections certain hazards in treatment may be and often have been accepted). One drug in common use against pinworms, piperazine, is both effective and safe. It has, however, the disadvantage that treatment must be continuous over a substantial period of time, for example at least one to two weeks.
In our companion application Serial No. 104,798, filed April 24, 1961, we have disclosed that various distilbazoles such as that shown in Formula I (where X is an anion) are highly effective in eliminating a variety of nematode parasites, including pinworms. This particular compound, unfortunately, is relatively toxic in mice and the therapeutic index is correspondingly low. While its toxicity is not constant from host to host and it may have therapeutic use in certain disorders, e.g. hookworm, especially N CH9 This anion does not contribute to the anthelmintic action and its identity is not important as long as it is pharmaceutically acceptable. Iodide, bromide, chloride, toluene sulfonate, and ethyl sulfate, for example, are convenient anions and essentially equivalent values for X.
Accordingly, the invention comprises a novel group of distilbazole compounds of the preceding formula and the administration of these compounds in the treatment of nematode infestations, particulary human pin-worms.
In Table I are shown the result of tests with illustrative compounds of this invention and of three close relatives, first in regard to toxicity (LD in mice and secondly in eliminating the pin-worm of mice, Syphacia obvelata. (This parasite has been found in past experience to be of particular value as vectors which indicate drugs useful against the human pin-worm.) It will be seen that the first three compounds of the table, having dimethylamino or diethylamino groups on the benzene rings have LD values of 2535 mg./kg. while high efficiency against pinworms requires /3 to /2 of that amount.
The six following compounds are active at about the same level, but have an entirely different order of toxicity (LD being over 1000 mg./kg. in four of the six cases). All of these compounds were administered as iodides wherefore differences in molecular weights were negligible as regards relative toxicity. When the alkyl group R is lengthened to the butyl stage, the consistent pattern of high efiiciency and low toxicity breaks down, i.e. one of these homologues is relatively ineffective and the other considerably more toxic (LD =300 mg./kg.).
These compounds are conveniently prepared by condensation of two mols of p-pyrrolidino or p-piperidinobenzaldehyde with a quaternary salt of 2,6-lutidine (in the diagram 11, R and X have the same values as above).
n o om solvents the usual metathetical conversions of anions (e.g. that of an iodide to a chloride by treatment with silver chloride) are rather unsatisfactory. It is consequently convenient to have as the anion of the lutidine quaternary salt that anion which is desired in the product. Again, conveniently, the anion may be that introduced by the alkyiating agent. Thus if one desires that in H R should be ethyl and X iodide, 2,6-lutidine is allrylated with ethyl iodide. If X- should be the ethylsulfate anion, alkylation would be with diethyl sulfate. Similarly, alkylation of 2,6-lutidine with propyl p-toluenesulfonate aflfords 2,6- dimethyl-l-propylpyridiniurn tosylate which is then condensed with p-pyrrolidinobenzaldehyde or p-piperidinobenzaldehyde to give 2,6-bis-p-pyrrolidino or piperidino styrylpyridine n-propyl tosylate.
Alternatively, metathetical interconversions are readily accomplished at this stage so that to make a Compound II where X is chloride, it is easy to convert 2,6- lutidine methiodide to the metho-chloride by warming with methanolic hydrogen chloride.
The compounds '11 are dark-colored crystals whose surface color ranges from dark red to almost black.
They melt with probable decomposition well above 200 and are sparingly soluble in virtually all solvents, the solutions being pinkish or reddish if sufficiently concentrated. In water so little material dissolves that the solvent is not visibly colored. The color is due to an intense but broad absorption band, approximately identical as between the individual compounds. The A max. is at about 495 mu (E =55,000-60,000) but intense absorption (E 40,000 or over) is manifest from about 460- 530 m The melting points being attended by decomposition are somewhat dependent on the rate of heating. Further, the dark color of the compounds renders precise observation of the melting points extremely difiicult. The data on melting points of the compounds II must, therefore, be regarded as only approximate. They are of little value for identification and of no value as criteria of purity.
EXAMPLE 1 Preparations .dissolved in 200 cc. of methanol and hydrogen chloride gas was run in until 20 g. had been absorbed. The solution was then warmed on the steam bath, most of the solvent being gradually distilled out. One hundred cc. of 10% methanolic hydrogen chloride was then added and the process repeated. Finally the flask was evacurated on the steam bath. The rather hydroscopic residue was the etho-chloride of 2,6-lutidine and was suitable for synthetic purposes without further manipulation.
EXAMPLE 2 N-phenylpyrr'oIidine.-A mixture of 216 g. of 1,4-dibromobutane, 500 cc. of methanol and 465 g. of aniline was refluxed for 5 hours at 100 C. Methanol was evaporated and 120 g. of sodium hydroxide (as 40-50% aqueous solution) was added to the residue. The organic layer was taken up in ether and dried over anhydrous 4, potassium carbonate. After removing potassium carbonate and ether the excess aniline was distilled in vacuo and saved, and the product was collected. N-phenylpyrrolidine boiled at 133-134 C. at 19 mm.; the yield was 130 g. (88-90%).
EXAMPLE 3 p-Pyrrolidinobenzaldehyde.To 32 cc. of dimethylfor-rnamide chilled in an ice bath was added 9 cc. (=16 g.) of phosphorus oxychloride over 10 minutes with stirring. To the chilled and stirred mixture 15 g. of N- phenylpyrrolidine was added dropwise during 15-30 minutes. The reaction mixture was heated for 2-2 /z hours at 100 C., then was cooled and poured onto 100 g. of ice. The aqueous solution was basified to pH 11 by the .addition of about 25 g. of sodium hydroxide (as 40-50% EXAMPLE 4 2,6-bis-(p-pyrrolidinostyryl) -1-ethylpyridinium iodide- A mixture containing 2.6 g. of 2,6-lutidine ethiodide, 100 cc. of methanol, 4.2 g. of p-pyrrolidinobenzaldehyde and 1 cc. of piperidine was refluxed on a steam bath. Insoluble solid precipitated and heavy bumping started in less than on hour. After 2 hours this product was collected (2 g.) and the filtrates were refluxed for 20 hours longer. A second crop of 2.5 g. was obtained and on standing another day or so the filtrates gave a third crop of one g. The total yield was 5.5 g. (-95%) in three crops, MP. 282-283 C. The product was nearly insoluble in hot methanol and was purified by washing several times with ether and then digesting one or two times with 10-20 times its weigh-t of hot methanol. Because it is difiicult to recrystallize it is desirable that nearly all insoluble impurities (dust, boiling stones, etc.) be removed from the easily purified reactants before the final con densation step and be kept out as much as possible thereafter.
On a larger scale bumping can become a major problem. In such cases a powerful stirrer should be used or the reaction-mixture should be held at 60-65" C. or below the boiling point of methanol.
When the p-pyrrolidinobenzaldehyde is condensed by the same procedure with 2,6-lutidine ethochloride, the product is 2,6-bis-(p-pyrrolidinostyryl) pyridine ethochloride which decomposes above 270 and on gross examination cannot be distinguished from the ethiodide. Diflerent values are obtained on analysis.
By the same procedures p-pyrrolidinobenzaldehyde was condensed with -2,6-lutidine methiodide and 2,6-lutidine-n-propiodide to give 2,6 bis (p-pyrrolidinostyryl) pyridine methiodide and propiodide. These compounds melted with decomposition at 295-7 and 265-7" respectively. Condensation of the aldehyde with 2,6-lutidinepropyl tosylate afforded 2,6-bis-(pyrrolidinostyryl) pyridine propyl tosylate which decomposes around 260".
Similarly p-piperidinobenzaldehyde was condensed with 2,6-lutidine methiodide, ethiodide and propiodide giving 2,6-bis-(piperidinostyryl) pyridine methiodide, ethiodide and propiodide which melt with decomposition at 222-5",
242-4 and 228-9 respectively.
TABLE I.ACTIVITIES AND TOXICITIES OF COMPOUNDS OF THE FORMULA Efiectiveness against Syphacia abuelata in mice LDgo, WRL No. RRN R mg. 'g.
(mice) Single Percent Mice dose worms cleared] mgjkg. removed Mice dosed 48-236 (CHmN H1 25 20 100 /5 1.5 100 5/5 97 7/13 5 92 2/13 2.5 51 0/6 61-2 (CHmN ch 35 100 3/3 10 97 5/9 7.5 92 1/6 5 86 2/6 2.5 69 1/6 60-434 (C1H3)2N- CH3 20 99 4/5 10 99 4/5 5 67 1/12 61-31 N CH3 1 000 20 96 3/6 10 92 2 6 5 so 2/6 61-32 N Cm: 1,350 2g 13g a 6 2/3 61-75 N CHZCHZCHS. 1,000 22 1 25g 10 84 3/6 61-26 N CH6 1,o00 20 100 3/3 13 99 6/9 10 98 3/9 5 88 0/9 61-143 N 01H, s00 20 100 6/6 10 100 6/6 5 83 2/4 61-144 N 01120112033- 450 20 100 6/6 10 96 4/6 5 90 2/6 What we claim is: 1. A compound of the formula fi (CE;),;NCH=CH OH=CH-N\ )CHz), 0m 011,
R X- wherein n has the values of 2 and 3, R is selected from 2,534,237 Cusic Dec. 19, 1950 the class consisting of the methyl, ethyl and n-propyl 2,890,982 Natt June 16, 1959 groups, and X- is an anion derived from a pharmaceutically acceptable acid. FOREIGN PATENTS s-(py y y y pyridinium 656,515 G ea Brit n Aug, 5
e. 3. 2,6-bis-(pyrrolidinostyryl)-1-ethylpyridinium iodide. OTHER REFERENCES g 'z'bls'(pyrrohdmostyryl) 1 Propylpyndlmum Welch et al.: Science, volume 105, pages 486-8, May 5 2,6-bis-(piperidinostyryl)-1-methylpyridinium iodide. ggg et Science volume 105 a e 496 Ma 9 6. 2,6-bis-(piperidinostyryl)-l-ethylpyridinium iodide. 1947 g y 26'b1S'(p1pendmostyryl)'l'p mp ylp yndm mm lodlde' Venkatararnan: The Chemistry of Synthetic Dyes, References Cited in the file of this patent volume II, pages 1172-33 and 1185, Academic Press Inc.,
UNITED STATES PATENTS New 1952' 1,994,170 Dabclow et a1. Mar. 12, 1935

Claims (1)

1. A COMPOUND OF THE FORMULA
US115996A 1961-04-24 1961-06-07 Anthelmintic distilbazoles and method Expired - Lifetime US3075975A (en)

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Application Number Priority Date Filing Date Title
NL277327D NL277327A (en) 1961-04-24
US115996A US3075975A (en) 1961-04-24 1961-06-07 Anthelmintic distilbazoles and method
GB22626/61A GB1009301A (en) 1961-04-24 1961-12-22 Styryl-pyridinium compounds, the preparation thereof, and pharmaceutical compositions thereof
DE19621470413 DE1470413A1 (en) 1961-04-24 1962-04-16 Quaternary ammonium compounds, their manufacture and pharmaceutical preparations
ES276612A ES276612A1 (en) 1961-04-24 1962-04-18 A method for the preparation of diestilizabol compounds (Machine-translation by Google Translate, not legally binding)
CH480662A CH413836A (en) 1961-04-24 1962-04-18 Process for the preparation of distilbazoles
DK179562AA DK104234C (en) 1961-04-24 1962-04-18 Process for the preparation of distilbazole compounds.
LU41596D LU41596A1 (en) 1961-04-24 1962-04-21
BR138334/62A BR6238334D0 (en) 1961-04-24 1962-04-23 A PROCESS FOR THE PREPARATION OF CATION DISTILBAZOL COMPOUNDS
FR895385A FR1320520A (en) 1961-04-24 1962-04-24 Quaternary salts of distilbazole derivatives
FR895386A FR1841M (en) 1961-04-24 1962-04-24 Medicinal product based on a quaternary salt derived from distilbazole.
OA52810A OA02352A (en) 1961-04-24 1967-03-11 Quaternary salts of distibazole derivatives.
MY196793A MY6700093A (en) 1961-04-24 1967-12-31 Styryl-pyridium compounds, the preparation thereof, and pharmaceutical compositions thereof

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US104798A US3085935A (en) 1961-04-24 1961-04-24 Method for the elimination of nematode infestations
US115996A US3075975A (en) 1961-04-24 1961-06-07 Anthelmintic distilbazoles and method

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BR (1) BR6238334D0 (en)
CH (1) CH413836A (en)
DE (1) DE1470413A1 (en)
DK (1) DK104234C (en)
ES (1) ES276612A1 (en)
FR (1) FR1841M (en)
GB (1) GB1009301A (en)
LU (1) LU41596A1 (en)
MY (1) MY6700093A (en)
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OA (1) OA02352A (en)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3883658A (en) * 1968-09-19 1975-05-13 Burroughs Wellcome Co Method of treating nematode infestations
WO2004078136A2 (en) * 2003-03-03 2004-09-16 Mycosol, Inc. Pyridinium salts, compounds and methods of use
WO2007056556A2 (en) * 2005-11-08 2007-05-18 Mycosol, Inc. Polyethylene glycol conjugates of pyridinium and thiazolium compounds and methods of using the same
US20130281392A1 (en) * 2012-04-20 2013-10-24 Merial Limited Parasiticidal compositions comprising benzimidazole derivatives, methods and uses thereof

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US1994170A (en) * 1930-09-20 1935-03-12 Agfa Ansco Corp Compound of the distyryl pyridinium salt series and its production
US2534237A (en) * 1950-12-19 B-haloxanthine salts of aminoalkyl
GB656515A (en) * 1947-04-02 1951-08-22 Gevaert Photo Producten Naamlo Improvements in and relating to cyanine and styryl dyestuffs or dye bases and to thepreparation thereof and to photographic emulsions containing the same
US2890982A (en) * 1956-10-30 1959-06-16 Norwich Pharma Co Method of combatting helminthiasis using nitro-furyl-acrylate derivatives

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2534237A (en) * 1950-12-19 B-haloxanthine salts of aminoalkyl
US1994170A (en) * 1930-09-20 1935-03-12 Agfa Ansco Corp Compound of the distyryl pyridinium salt series and its production
GB656515A (en) * 1947-04-02 1951-08-22 Gevaert Photo Producten Naamlo Improvements in and relating to cyanine and styryl dyestuffs or dye bases and to thepreparation thereof and to photographic emulsions containing the same
US2890982A (en) * 1956-10-30 1959-06-16 Norwich Pharma Co Method of combatting helminthiasis using nitro-furyl-acrylate derivatives

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3883658A (en) * 1968-09-19 1975-05-13 Burroughs Wellcome Co Method of treating nematode infestations
JP4742028B2 (en) * 2003-03-03 2011-08-10 マイコソル，インコーポレイテッド Pyridinium salts, compounds and methods of use
WO2004078136A2 (en) * 2003-03-03 2004-09-16 Mycosol, Inc. Pyridinium salts, compounds and methods of use
WO2004078136A3 (en) * 2003-03-03 2004-12-16 Mycosol Inc Pyridinium salts, compounds and methods of use
US8124626B2 (en) 2003-03-03 2012-02-28 Mycosol, Inc. Methods of treating inflammations and infections with pyridinium salts
US7220761B2 (en) 2003-03-03 2007-05-22 Mycosol, Inc. Compounds and methods for controlling fungi, bacteria and insects
JP2007525441A (en) * 2003-03-03 2007-09-06 マイコソル，インコーポレイテッド Pyridinium salts, compounds and methods of use
US7547444B1 (en) 2003-03-03 2009-06-16 Mycosol, Inc. Methods for controlling fungi and bacteria
US7820696B2 (en) 2003-03-03 2010-10-26 Mycosol, Inc. Compounds and methods for controlling fungi, bacteria and insects
WO2007056556A3 (en) * 2005-11-08 2007-10-25 Mycosol Inc Polyethylene glycol conjugates of pyridinium and thiazolium compounds and methods of using the same
US20110053987A1 (en) * 2005-11-08 2011-03-03 Selph Jeffrey L Pyridinium and thiazolium conjugates including polyethylene glycols and methods of using the same
WO2007056556A2 (en) * 2005-11-08 2007-05-18 Mycosol, Inc. Polyethylene glycol conjugates of pyridinium and thiazolium compounds and methods of using the same
US8247571B2 (en) * 2005-11-08 2012-08-21 Mycosol, Inc. Pyridinium and thiazolium conjugates including polyethylene glycols and methods of using the same
US20130281392A1 (en) * 2012-04-20 2013-10-24 Merial Limited Parasiticidal compositions comprising benzimidazole derivatives, methods and uses thereof
US9000187B2 (en) * 2012-04-20 2015-04-07 Merial, Inc. Parasiticidal compositions comprising benzimidazole derivatives, methods and uses thereof

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FR1841M (en) 1963-06-04
MY6700093A (en) 1967-12-31
CH413836A (en) 1966-05-31
ES276612A1 (en) 1962-08-01
BR6238334D0 (en) 1973-05-17
NL277327A (en)
DK104234C (en) 1966-04-25
DE1470413A1 (en) 1969-07-17
LU41596A1 (en) 1962-10-22
GB1009301A (en) 1965-11-10
OA02352A (en) 1970-05-05

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