Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
  • C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
  • C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
  • C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
  • C07D251/16—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to only one ring carbon atom
  • C07D251/18—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to only one ring carbon atom with nitrogen atoms directly attached to the two other ring carbon atoms, e.g. guanamines
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
  • C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
  • C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
  • C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
  • C07D251/40—Nitrogen atoms
  • C07D251/54—Three nitrogen atoms
  • C07D251/70—Other substituted melamines
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
  • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
  • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
  • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
  • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
  • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
• • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
  • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
  • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
  • F16K31/00—Actuating devices; Operating means; Releasing devices
  • F16K31/12—Actuating devices; Operating means; Releasing devices actuated by fluid
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01L—MEASURING FORCE, STRESS, TORQUE, WORK, MECHANICAL POWER, MECHANICAL EFFICIENCY, OR FLUID PRESSURE
  • G01L11/00—Measuring steady or quasi-steady pressure of a fluid or a fluent solid material by means not provided for in group G01L7/00 or G01L9/00

Definitions

• the new compounds exhibit anti-inflammatory and antiatherosclerotic activity.
• This invention relates to s-triazine derivatives of the formula wherein R is pyrrolidino, piperidino, 2-ketopiperazine-4- yl or NR R R being hydrogen or straight or branched alkyl of from 1-6 carbon atoms and R being cycloalkyl or straight or branched alkyl of from 1-6 carbon atoms.
• the acid addition salts of the new compounds with organic and inorganic acids, such as hydrochloric acid, maleic acid, tartaric acid, citric acid, and lactic acid are also embraced.
• inventive compounds can be prepared according to the following reaction scheme:
• Each value is the average value obtained in testing 5 mice.
• mice Activated RES on mice were induced by administration of typhoid-paratyphoid-vaccine every other day. Typhoidparatyphoid-vaccine was injected intravenously in an amount of 0.1 m1./ animal at the tail vein.
• the inhibitory percentage was determined by carbon phagocytosis of RES and calculated relative to a control which is defined as 100.
• inventive compounds were administered, 300- mg./ kg., orally one hour before injection of typhoid-paratyphoid-vaccine.
• the s-triazine derivatives of the present invention exhibit either anti-inflammatory activity or anti-atherosclerotic activity. These activities have been satisfactorily demonstrated in animal tests.
• 2-amino-4- phenethylamino-G-(Z ketopiperazine-4 yl)-s-triazine (Example 1), when administered orally to rabbits, caused TAB LE II Ilntluenee of the Example 1 Compound on Serum Cholesterol, Cholestrol Content of Aorta and Grade oi Atherosclerotie Plaques of Rabbits which were fed a High Cholesterol Diet for Days] N orma Cholesterol diet group diet Percentage of drug in diet Number of rabbits Serum cholesterol (mg.
• Example 1 The remarkable inhibitory effect of the Example 1 compound was indicated in the average plaque grade of the aortas and the cholesterol content of the aorta was significantly decreased.
• a different experimental group of rabbits received a cholesterol diet for 80 days and then was put on normal diet.
• Example 1 compound in a concentration of 0.1% was introduced at that time into the diet of one group.
• the control group was fed a normal diet. These animals were then killed at intervals up to 43 days thereafter.
• the aortas were removed and examined histologicaly with a number of different stains.
• Example 1 The anti-inflammatory activity of the Example 1 compound was demonstrated by the following:
• Example 1 compound When 100 mg./kg./day of the Example 1 compound was orally administered to rats immunized by heat killed Tubercli-Bacilli in mineral oil, for 4 days, 24% inhibition of passive cutaneous anaphlaxis reaction was observed, as compared with that of the control group.
• Example 1 compound When 300 mg./kg. of the Example 1 compound was administered to rats orally, inflammatory edema caused by carrageenin in the paw was about 25% less than the value of the control.
• the Example 1 compound has a low toxicity. No mortality occurred in the oral administration of over 20 g./kg. of the Example 1 compound to mice.
• inventive triazine derivatives Various cortison-inhibitory activities were also observed in the inventive triazine derivatives. Therefore, the inventive compounds are not only pharmacologically useful as an anti-atherosclerotic agent, but they also act as an anti-inflammatory agent in place of steroidal anti-inflammatory agents.
• Phenethylamine (6.1 g.) is added, with stirring, to a mixture of 2-amino-4,6-dichloro-s-triazine (8.2 g.) in Water (100 ml.). The mixture is slowly heated to reflux temperature and the refluxing temperature is maintained for 2 hours. During this time, sodium carbonate (2.7
• the syrup (7.0 g.) is dissolved in methanol (40 ml.) and added to a solution of maleic acid (2.0 g.) in methanol (10 ml.) to yield a crystalline precipitate.
• the precipitate is collected by filtration and recrystallized from methanol to give 2-amino 4 phenethylamino-6-pyrrolidino-s-triazine maleate as colorless needles, M.P. 149- 150 C.
• the yield is 2.1 g.
• the syrup (6.0 g.) is dissolved in methanol (40 ml.) and added to a solution of maleic acid (1.7 g.) in methanol 10 ml.) to yield a crystalline precipitate.
• the precipitate is collected by filtration and recrystallized from methanol to give 2-amino-4-phenethylamino-G-piperidinos-triazine maleate as white crystals, M.P. 164-166 C.
• the yield is 3.0 g.
• the syrup (6.2 g.) is dissolved in methanol (20 ml.) and added to a solution of maleic acid (1.7 g.) in methanol (10 ml.) to yield a white precipitate.
• the precipitate is collected by filtration and recrystallized from methanol to give 2-amino-4-phenethylamino-6-ethylamino-s-triazine maleate as white crystal powder, M.P. l6ll62.5 C.
• the yield is 0.8 g.
• the syrup (6.8 g.) is dissolved in methanol (30 m1.) and added to a solution of maleic acid (1.7 g.) in methanol. The solvent is evaporated from the mixture to give a residue. The residue is recrystallized from benzene to give 2-amino 4 phenethylamino-6-di-n-propylamino-s-triazine maleate as white crystals, M.P. 118120 C. The yield is 5.0 g.
• the syrup (3.1 g.) is dissolved in methanol (50 ml.) and added to a solution of maleic acid (1.1 g.) in methanol 30 ml.) to yield a crystalline precipitate.
• the precipitate is collected by filtration and recrystallized from methanol to give 2 amino-4-phenetliylamino-6-cyclohexylamino-striazine maleate as white crystals, M.P. C. (dec.).
• the yield is 1 g.
• the syrup (8.0 g.) is dissolved in methanol (50 ml.) and added to a solution of maleic acid (2.9 g.) in methanol (30 ml.) to yield a crystalline precipitate.
• the precipitate is collected by filtration and recrystallized from methanol to give 2 amino-4-phenethylamino-6-n-hexylamino-s-triazine maleate as white crystals, M.P. 139-l42 C.
• the yield is 0.7 g.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• Engineering & Computer Science (AREA)
• General Engineering & Computer Science (AREA)
• Life Sciences & Earth Sciences (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Physics & Mathematics (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Medicinal Chemistry (AREA)
• General Physics & Mathematics (AREA)
• Mechanical Engineering (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Plural Heterocyclic Compounds (AREA)

Applications Claiming Priority (6)

Publications (1)

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Cited By (3)

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• 1969
  • 1969-01-16 BE BE726947D patent/BE726947A/xx unknown
  • 1969-01-16 BE BE726948D patent/BE726948A/xx unknown
  • 1969-02-07 FR FR6902985A patent/FR2005901A1/fr not_active Withdrawn
  • 1969-02-11 FR FR6903183A patent/FR2005902A1/fr not_active Withdrawn
  • 1969-02-14 DE DE1907589A patent/DE1907589C3/de not_active Expired
  • 1969-03-14 DE DE1913154A patent/DE1913154C3/de not_active Expired
  • 1969-03-25 GB GB1252870D patent/GB1252870A/en not_active Expired
  • 1969-03-25 GB GB1250971D patent/GB1250971A/en not_active Expired
• 1971
  • 1971-06-15 US US00153395A patent/US3759911A/en not_active Expired - Lifetime
  • 1971-06-15 US US00153396A patent/US3758471A/en not_active Expired - Lifetime

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