Classifications

• • 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)

Priority Applications (14)

Applications Claiming Priority (2)

Publications (1)

Family

ID=26801948

Family Applications (1)

Country Status (13)

Cited By (4)

Citations (4)

• 0
  • NL NL277327D patent/NL277327A/xx unknown
• 1961
  • 1961-06-07 US US115996A patent/US3075975A/en not_active Expired - Lifetime
  • 1961-12-22 GB GB22626/61A patent/GB1009301A/en not_active Expired
• 1962
  • 1962-04-16 DE DE19621470413 patent/DE1470413A1/de active Pending
  • 1962-04-18 ES ES276612A patent/ES276612A1/es not_active Expired
  • 1962-04-18 DK DK179562AA patent/DK104234C/da active
  • 1962-04-18 CH CH480662A patent/CH413836A/de unknown
  • 1962-04-21 LU LU41596D patent/LU41596A1/xx unknown
  • 1962-04-23 BR BR138334/62A patent/BR6238334D0/pt unknown
  • 1962-04-24 SE SE451262A patent/SE217920C1/xx unknown
  • 1962-04-24 FR FR895386A patent/FR1841M/fr not_active Expired
• 1967
  • 1967-03-11 OA OA52810A patent/OA02352A/xx unknown
  • 1967-12-31 MY MY196793A patent/MY6700093A/xx unknown

Patent Citations (4)

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