US3851060A - Composition and methods for treating nematode infections - Google Patents

Composition and methods for treating nematode infections Download PDF

Info

Publication number
US3851060A
US3851060A US00215926A US21592672A US3851060A US 3851060 A US3851060 A US 3851060A US 00215926 A US00215926 A US 00215926A US 21592672 A US21592672 A US 21592672A US 3851060 A US3851060 A US 3851060A
Authority
US
United States
Prior art keywords
pyrryl
vinyl
dimethyl
formula
methiodide
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US00215926A
Other languages
English (en)
Inventor
R Burrows
A Phillips
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
SmithKline Beecham Corp
Original Assignee
Burroughs Wellcome Co USA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to GB1215869A priority Critical patent/GB1304174A/en
Priority to DE19702010490 priority patent/DE2010490A1/de
Priority to NL7003246A priority patent/NL7003246A/xx
Priority to BE746998D priority patent/BE746998A/xx
Priority to CA076,734A priority patent/CA960667A/en
Priority to CH336870A priority patent/CH555857A/de
Priority to SE03000/70A priority patent/SE368709B/xx
Priority to CH1263372A priority patent/CH574958A5/xx
Priority to FR7008340A priority patent/FR2096715B1/fr
Application filed by Burroughs Wellcome Co USA filed Critical Burroughs Wellcome Co USA
Priority to US00215926A priority patent/US3851060A/en
Application granted granted Critical
Publication of US3851060A publication Critical patent/US3851060A/en
Assigned to WELLCOME ANIMAL HEALTH, INC. reassignment WELLCOME ANIMAL HEALTH, INC. ASSIGNMENT OF ASSIGNORS INTEREST. Assignors: BURROUGHS WELLCOME CO.
Assigned to BURROUGHS WELLCOME CO., A CORP OF NORTH CAROLINA reassignment BURROUGHS WELLCOME CO., A CORP OF NORTH CAROLINA ASSIGNMENT OF ASSIGNORS INTEREST. Assignors: WELLCOME ANIMAL HEALTH INC
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/323—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to the ring nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/333—Radicals substituted by oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/337—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/54—Quaternary phosphonium compounds
    • C07F9/5407—Acyclic saturated phosphonium compounds
    • 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
    • C09B23/10—The polymethine chain containing an even number of >CH- groups
    • C09B23/105—The polymethine chain containing an even number of >CH- groups two >CH- groups
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
    • H01L23/00—Details of semiconductor or other solid state devices
    • H01L23/48—Arrangements for conducting electric current to or from the solid state body in operation, e.g. leads, terminal arrangements ; Selection of materials therefor
    • H01L23/488—Arrangements for conducting electric current to or from the solid state body in operation, e.g. leads, terminal arrangements ; Selection of materials therefor consisting of soldered or bonded constructions
    • H01L23/498—Leads, i.e. metallisations or lead-frames on insulating substrates, e.g. chip carriers
    • H01L23/49827—Via connections through the substrates, e.g. pins going through the substrate, coaxial cables
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
    • H01L2924/00—Indexing scheme for arrangements or methods for connecting or disconnecting semiconductor or solid-state bodies as covered by H01L24/00
    • H01L2924/0001—Technical content checked by a classifier
    • H01L2924/0002—Not covered by any one of groups H01L24/00, H01L24/00 and H01L2224/00

Definitions

  • the compounds are useful in having activity against parasitic nematodes infecting warm-blooded animals.
  • This invention relates to quaternary ammonium salts, their synthesis, pharmaceutical compositions containing them, and their use as therapeutic agents.
  • R is alkyl or is an optionally substituted phenyl group
  • Z is phenyl, p-halophenyl, p-alkoxyphenyl, biphenylyl, p-alkoxybiphenylyl or naphthyl
  • X is the anion of a pharmaceutically acceptable acid
  • the compounds of formula (I) have been found activeagainst parasitic nematodes, especially pinworms although the compounds also have activity against other nematodes such as whipworms, hookworms, etc. Thus they have been found active against Syphacia obvelata in mice, a screening organism for the human pinworm, Enterobius vermicularis, both organisms having similar lifecycles. Also, they have activity against Aspiculuris tetraptera in mice.
  • the compounds have high LD doses which, together with their good anthelmintic activities at low doses, gives them a high therapeutic index.
  • Z is biphenylyl
  • Other preferred compounds are those in which Z is p-alkoxyphenyl, the alkoxy having 1 to 6 carbon atoms, that is methoxy to hexoxy.
  • R is an alkyl group, it has 1 to 6 carbon atoms, that is methyl to hexyl.
  • R is a phenyl group, it may be substituted by one or more groups such as halogen (that is, chlorine, bromine,
  • references in the specification and claims to pyrrylvinylthiazolinm salts of formula (I) mean salts of a pharmaceutically acceptable acid.
  • the compounds of formula (I) may be made by any method known for preparing compounds of an analogous chemical structure. Thus, they may be prepared by the reaction of a thiazolium compound of the formula (II) wherein Z, R and X are as defined above.
  • the reaction is preferably carried out in the presence of a basic catalyst such as piperidine, but other bases of comparable or greater basic strength may be used, for example, amines (pyrrolidine, N-methylpyrrolidine) or an alkali metal hydroxide or an alkoxide.
  • the reaction is conveniently carried out in the presence of a liquid medium which is, or contains, a polar liquid, in which the reactants may be dissolved or suspended in a finely divided form.
  • the liquid medium for the reaction is preferably a lower alcohol (optionally containing water) such as methanol or ethanol, or' may be some other polar medium not reactive to the reactants such as dimethyl sulphoxide or sulfolane.
  • the reaction is preferably conducted at a temperature from C. to the boiling point of the reaction mixture.
  • the intermediate 2,3-dimethy1-4-Z-thiazoliurn salts of formula (II) may be prepared by the following sequence of reactions, the last step providing for the quaternisation of the 2-methyl-4 Z-thiazole of formula (VI) by a methyl derivative CH A:
  • A is a nucleophilic group or atom, for example, chlorine, bromine or iodine, or a methosulphate or p-toluenesulphonate group.
  • This reaction proceeds via an intermediate thioimidate of formula (IX) ona S CH1 z-bo from wherein Z and R are as defined above, and this thioimidate itself, if desired, may be isolated and then converted to a compound of formula (I) as described below.
  • the compounds of formula (I) are formed by the reaction of the phenacyl derivative of formula (VII) and the thioamide of formula (VIII) under conditions which convert the thioimidate intermediate (IX) to a compound of formula (I). In general, heating the reactants, or reacting them in the presence of an acid, will tend to form the compounds of formula (I). A temperature of 80 to 150 C. is conveniently employed to effect a rapid conversion to the compounds of formula (I).
  • the acid may be a mineral acid such as hydrochloric or hydrobromic acid and preferably corresponds to the nucleophilic group or atom A which provides the anion X- of formula (I).
  • the reaction is preferably performed in the presence of a polar liquid medium, for example, a lower alkanol such as ethanol or butanol, or a water/butanol mixture.
  • a polar liquid medium for example, a lower alkanol such as ethanol or butanol, or a water/butanol mixture.
  • the opti mum reaction conditions for forming the compounds of formula (I) vary according to the nature of the thioimidate intermediate, the group A and the liquid medium employed.
  • the thioimidates of formula (IX) and their acid addition salts may themselves be converted to the compounds of formula (I) by treatment with an acid, preferably a mineral acid, for example, hydrochloric or hydrobromic acid, which should preferably correspond to the thioim-idate salt, if used, and to the desired thiazolium salt of formula (I).
  • the acid addition salts of the thioimidates of formula (IX) may also be converted to the compounds of formula (I) by heating the salts, preferably the hydrochloric or hydrobromic acid addition salts.
  • the reaction is preferably conducted in a polar liquid medium, for example, a lower alkanol such as butanol, conveniently at a temperature of to 150 C.
  • the activity against nematodes of the compounds of for mula (I) resides in the cation, and the nature of the anion X is unimportant providing that the salt is pharmaceutically acceptable.
  • suitable salts are the halides, sulphonates, sulphates and alkyl sulphates.
  • the iodide, methosulphate and p-toluenesulphonate salts are preferred since they can be conveniently introduced in the quaternisation step by the use of methyl iodide, dimethylsulphate and methyl p-toluenesulphonate.
  • the bromide salts may be prepared by the use of methyl bromide.
  • salts may be prepared by conventional procedures, for example, by replacing the anion by double decomposition of either the 2,3-dimethyl-4-Z-thiazolium salt or the 2-(R-2,5-dimethyl-3-pyrryl)-3 methyl-4-Z-thiazolium salt.
  • the chloride salts may be prepared from the iodide salts by shaking the latter with silver chloride in alkanolic solution; and the chloride and bromide salts may be converted to the iodide salts by reaction with potassium iodide, either before or after their isolation from the reaction mixture.
  • the compounds of formula (I) are conveniently administered in pharmaceutical compositions comprising the compounds and an acceptable carrier therefor.
  • Any well known type of pharmaceutical composition may be used for this purpose, but compositions for oral use are preferred.
  • compositions for administration of the compounds of formula (I) in dry solid form they may be presented as capsules, granules, pills, powders, tablets, boluses, or in a gelatin cube, containing the desired amount of the compound distributed in such carriers as are usually employed.
  • the compositions are prepared in general by intimately and uniformly mixing the active ingredient with the carrier which may comprise one or more diluents, fillers, disintegrating agents and binders.
  • Boluses and tablets may be compounded by techniques well known in the art, for example, by compression on a tabletting machine.
  • the tablets may be formed so as to disintegrate rapidly, or to provide a prolonged or delayed action, or to provide a predetermined release of the active ingredient at successive intervals.
  • the tablets also may be coated.
  • Capsules are readily prepared by combining the active ingredient with any desired excipient and filling into the capsule.
  • the compounds of formula (I) may also be administered in a liquid preparation or as a component of the feed of the animal.
  • Liquid preparations may comprise a suspension or solution of the active ingredient in water or in a vegetable or mineral oil or an emulsion thereof.
  • the liquid carrier itself may consist of one or more ingredients, for example, liquid diluents, buffers, bacteriostats, sweeteners, colouring matter, dispersing agents, suspending agents and emulsifiers.
  • the normal unit dose range for the compounds of formula (I) is from 5 to mg. cation/kg. body weight of the animal being treated.
  • the preferred unit dose range is 5 to 25 mg./kg.
  • the invention thus also provides a method for the preparation of the compounds of formula (I) as hereinbefore described.
  • the invention therefore further provides a method for the treatment of a nematode infection in warm-blooded animals or mammals (for example dogs, cats and humans) comprising the administration (preferably oral) of an effective amount of a compound of formula (I) to the host of the infection. It also provides a pharmaceutical composition comprising a compound of formula (I) together with a pharmaceutically acceptable carrier therefor, and a method of preparing such a composition by admixture of the components.
  • the invention also provides a pharmaceutical composition for use as an anthelmintic which comprises essentially an effective amount of a compound of formula (I) in combination with a pharmaceutically acceptable carrier therefor.
  • 1-phenyl-2,S-dimethylpyrrole 3 carboxaldehyde was prepared as follows. Aniline (19 g., 0.2M), acetonylacetone (23 g., 0.2M) and glacial acetic acid (2 cc.) were mixed and heated for a half to one hour on a steam bath. Upon cooling white crystals formed which were recrystallised from ethanol to give 2,5-dimethyl-l-phenylpyrrole (31 to 33 g., 95%+ yield) melting at 51 to 52 C.
  • EXAMPLE 4 2- ⁇ fl-(1,2,5-trimethyl-3-pyrryl)vinyl ⁇ -3-methyl-4pbromophenylthiazolium bromide under reflux.
  • the yellow solid which soon came out of solution was collected after 1 hour, and recrystallised from methanol to give deep yellow prisms, m.p. 180 (decomp.), of p-bromophenacyl-N-methyl-3-(1,2,5-trimethylpyrrol-3-yl)acrylothioimidate hydrobromide.
  • EXAMPLE 5 A tablet was made from the following ingredients:
  • a paste was prepared of (i) and (ii) using (iii) and (iv). Ingredient (v) was dissolved in the greater part of (vi), using heat, and the solution used to dilute the paste previously prepared. The volume of the resultant suspension was adjusted using the rest of the purified water.
  • An orally ingestible nematode infection treatment composition for mammals which comprises a therapeutically acceptable solid carrier and an effective non-toxic nematode infection treatment amount of a salt of the formula zmqjaacnill kHz
  • R is selected from the class consisting of alkyl having 1 to 6 carbon atoms, and phenyl optionally substituted by one or more halogen atoms, alkyl groups having 1 to 4 carbon atoms or alkoxy groups having 1 to 4 carbon atoms
  • Z is selected from the class consisting of phenyl, p-halophenyl, p-alkoxyphenyl where the alkoxy has 1 t0 6 carbon atoms, biphenylyl, p-alkoxybiphenylyl where the alkoxy has 1 to 6 carbon atoms, and naphthyl
  • X- is the anion of a pharmaceutically acceptable acid.
  • composition according to claim 1 wherein Z is selected from the class consisting of biphenylyl, p-alkoxybiphenylyl, and naphthyl.
  • composition according to claim 1 in which the salt is 2 [;3-(l-ethyl 2,5 dimethyl 3 pyrryl)vinyl]- 3 methyl 4 p biphenylylthiazolium cation with the anion of a pharmaceutically acceptable acid.
  • composition according to claim 1 in which the salt is 2-[fl-(1-phenyl 2,5 dimethyl 3 pyrryl)vinyl]- 3 methyl 4 p biphenylylthiazolium cation with the anion of a pharmaceutically acceptable acid.
  • composition according to claim 1 in which the salt is 2-[p(1-p-chlorophenyl 2,5 dimethyl-3-pyrryl) vinyl] 3 methyl 4 p biphenylylthiazolium cation with the anion of a pharmaceutically acceptable acid.
  • composition according to claim 6 wherein the anion is iodide.
  • composition according to claim 7 wherein the anion is iodide.
  • composition according to claim 8 wherein the anion is iodide.
  • composition according to claim 9 wherein the anion is iodide.
  • a method for the treatment of a nematode infection in a mammal which comprises orally administering to the nematode infected mammal an effective non-toxic nematode infection treatment dose of a salt of the formula J TCHHLI where R is selected from the class consisting of alkyl having 1 to 6 carbon atoms and phenyl optionally substituted by one or more halogen atoms, alkyl groups having 1 to 4 carbon atoms or alkoxy groups having 1 to 4 carbon atoms; Z is selected from the class consisting of phenyl, phalophenyl, p-alkoxyphenyl where the alkoxy has 1 to 6 carbon atoms, biphenylyl, p-alkoxybiphenylyl where the alkoxy has 1 to 6 carbon atoms, and naphthyl; and X" is the anion of a pharmaceutically acceptable acid.
  • Z is selected from the class consisting of biphenylyl, p-alkoxybiphenylyl, and naphthyl.
  • Z is selected from the class consisting of phenyl and p-alkoxyphenyl.
  • Z is selected from the class consisting of biphenylyl and p-halophenyl
  • R is selected from the class consisting of alkyl and optionally substituted phenyl.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Condensed Matter Physics & Semiconductors (AREA)
  • General Physics & Mathematics (AREA)
  • Engineering & Computer Science (AREA)
  • Computer Hardware Design (AREA)
  • Microelectronics & Electronic Packaging (AREA)
  • Power Engineering (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
US00215926A 1969-03-07 1972-01-06 Composition and methods for treating nematode infections Expired - Lifetime US3851060A (en)

Priority Applications (10)

Application Number Priority Date Filing Date Title
GB1215869A GB1304174A (de) 1969-03-07 1969-03-07
DE19702010490 DE2010490A1 (de) 1969-03-07 1970-03-05 Heterocyclische Verbindungen, ihre Herstellung und Verwendung
CA076,734A CA960667A (en) 1969-03-07 1970-03-06 Heterocyclic compounds and their synthesis
CH336870A CH555857A (de) 1969-03-07 1970-03-06 Verfahren zur herstellung von pyrrylvinylthiazoliumsalzen.
SE03000/70A SE368709B (de) 1969-03-07 1970-03-06
CH1263372A CH574958A5 (de) 1969-03-07 1970-03-06
NL7003246A NL7003246A (de) 1969-03-07 1970-03-06
BE746998D BE746998A (fr) 1969-03-07 1970-03-06 Composes heterocycliques et leur synthese
FR7008340A FR2096715B1 (de) 1969-03-07 1970-03-09
US00215926A US3851060A (en) 1969-03-07 1972-01-06 Composition and methods for treating nematode infections

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB1215869 1969-03-07
US1594470A 1970-03-02 1970-03-02
US00215926A US3851060A (en) 1969-03-07 1972-01-06 Composition and methods for treating nematode infections

Publications (1)

Publication Number Publication Date
US3851060A true US3851060A (en) 1974-11-26

Family

ID=27256795

Family Applications (1)

Application Number Title Priority Date Filing Date
US00215926A Expired - Lifetime US3851060A (en) 1969-03-07 1972-01-06 Composition and methods for treating nematode infections

Country Status (9)

Country Link
US (1) US3851060A (de)
BE (1) BE746998A (de)
CA (1) CA960667A (de)
CH (2) CH574958A5 (de)
DE (1) DE2010490A1 (de)
FR (1) FR2096715B1 (de)
GB (1) GB1304174A (de)
NL (1) NL7003246A (de)
SE (1) SE368709B (de)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007056340A2 (en) * 2005-11-08 2007-05-18 Mycosol, Inc. Disinfectant and antiseptic pyridinium and thiazolium compounds and methods of using the same
US20080009416A1 (en) * 2004-12-17 2008-01-10 Mycosol, Inc. Thiazolium compounds and uses thereof

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4298743A (en) * 1979-09-11 1981-11-03 Merck & Co., Inc. 4-(Substituted phenyl thiazolyl)-3-hydroxy-3-pyrroline-2,5-diones

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3390148A (en) * 1965-07-28 1968-06-25 Pfizer & Co C Novel thiazine and thiazoline anthelmintic agents
GB1244961A (en) * 1967-09-22 1971-09-02 Burroughs Wellcome Co Thiazole derivatives

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080009416A1 (en) * 2004-12-17 2008-01-10 Mycosol, Inc. Thiazolium compounds and uses thereof
WO2007056340A2 (en) * 2005-11-08 2007-05-18 Mycosol, Inc. Disinfectant and antiseptic pyridinium and thiazolium compounds and methods of using the same
WO2007056340A3 (en) * 2005-11-08 2008-04-17 Mycosol Inc Disinfectant and antiseptic pyridinium and thiazolium compounds and methods of using the same

Also Published As

Publication number Publication date
FR2096715B1 (de) 1974-02-01
CH555857A (de) 1974-11-15
FR2096715A1 (de) 1972-02-25
DE2010490A1 (de) 1970-09-24
BE746998A (fr) 1970-09-07
CA960667A (en) 1975-01-07
CH574958A5 (de) 1976-04-30
SE368709B (de) 1974-07-15
GB1304174A (de) 1973-01-24
NL7003246A (de) 1970-09-09

Similar Documents

Publication Publication Date Title
US5462959A (en) 4-aryl-imidazole derivatives
CS390691A3 (en) Olefinic 1h-imidazo-(4,5-c)quinolin-4-amines
CA1257269A (en) Furo-(3,4-c)-pyridine derivatives preparation thereof and therapeutic compositions containing the same
JPS63146871A (ja) ベンゾイミダゾ−ル誘導体
EP0070518A2 (de) Imidazoquinoxalin-Verbindungen
DK157932B (da) 1,3-dihydro-6-methyl-furo-(3,4-c)-pyridin-derivater og farmaceutiske acceptable salte deraf samt farmaceutisk praeparat indeholdende disse
JPH0238591B2 (de)
IE47139B1 (en) 4-substituted-pyrazoles
NO147879B (no) Analogifremgangsmaate for fremstilling av terapeutisk virksomme 2-substituerte benzimidazoler
EP1142885A1 (de) Neue 2-(n-cyanimino)thiazolidin-4-on derivate
US3851060A (en) Composition and methods for treating nematode infections
US3579529A (en) Heterocyclic compounds
JPS61148164A (ja) ５−アルキル−１−フエニル−２−ピペラジノアルキルピラゾリン−３−オン−化合物、その製法およびこれを含有する抗アレルギ−作用を有する薬剤
US3444175A (en) Certain picolylmethyl sulfones
US3772287A (en) Pyrrylvinylthiazolium derivatives
CZ284238B6 (cs) Substituované beta-diketony, způsob jejich výroby a farmaceutický přípravek, který je obsahuje
EP0592664A1 (de) Neues diphenylthiazol-derivat
JPS5839668A (ja) １，５−ジフエニルピラゾリン−３−オン化合物、その製造法及び該化合物を含有する、抗アレルギ−作用を有する医薬品
JP2726999B2 (ja) イミダゾ［２，１−ｂ］ベンゾチアゾール誘導体及び該化合物を有効成分とする抗潰瘍剤
GB2154583A (en) pyrimidobenzthiazoles
JPH0377191B2 (de)
JPS60501207A (ja) 化合物
JPS6216469A (ja) ２−置換シクロヘプトイミダゾ−ル誘導体、抗潰瘍剤及びその製造方法
IL33986A (en) Substituted thiazolium salts,their preparation and pharmaceutical compositions containing them
IL30742A (en) Therapeutic thiazole quaternary ammonium salts

Legal Events

Date Code Title Description
AS Assignment

Owner name: WELLCOME ANIMAL HEALTH, INC. 520 WEST 21ST ST., KA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:BURROUGHS WELLCOME CO.;REEL/FRAME:004219/0926

Effective date: 19831224

AS Assignment

Owner name: BURROUGHS WELLCOME CO. 3030 CORNWALLIS ROAD, RESEA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:WELLCOME ANIMAL HEALTH INC;REEL/FRAME:004324/0915

Effective date: 19840830