Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
  • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
  • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
  • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
  • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
  • C07D239/52—Two oxygen atoms
  • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
  • C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
  • C07D239/557—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms, e.g. orotic acid
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D339/00—Heterocyclic compounds containing rings having two sulfur atoms as the only ring hetero atoms
  • C07D339/02—Five-membered rings
  • C07D339/04—Five-membered rings having the hetero atoms in positions 1 and 2, e.g. lipoic acid
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D473/00—Heterocyclic compounds containing purine ring systems
  • C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
  • C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
  • C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
  • C07D473/08—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1 and 3, e.g. theophylline
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
  • C07H23/00—Compounds containing boron, silicon, or a metal, e.g. chelates, vitamin B12

Definitions

• the present invention concerns new compounds of antiacidotic action such as the derivatives of tris (hydroxymethyl) amiuomethane, of important therapeutic applications.
• Nahas introduced the organic amines, among whichby its efficacy and non-toxicitythe tris (hydroxymethyl) aminomethane or THAM, which not only acts as a plasmatic buffer but also as an intracellular buffer.
• the mixture is constantly and vigorously agitated until a limpid liquid is obtained which is dropped, still scalding, into steel trays and, finally, is subjected to vacuum desiccation to preserve from moisture.
• the desiccated product must be manipulated rapidly and in a very dry medium as it is very hygroscopic. In this way are obtained some 145 g. of tris (hydroxymethyl) aminomethane theophylline acetate.
• EXAMPLE 4 15.8 g. of tris (hydroxymethyl) aminomethane hydrochloride are dissolved in the smallest possible quantity of water and 22.8 g. of sodium thioctate are previously added, dissolved in the smallest possible quantity of water.
• EXAMPLE 5 4 The product thus obtained is a microcrystalline powder, soluble in water and in alcohol and insoluble in ether.
• the LD 50 of tris (hydroxymethyl) aminomethane theophylline acetate in albino mice by oral route is 4.05:0.174 g./kg. and 2.45 i0.145 g./kg. by intravenous route.
• the LD 50 is 1600:168 mg./kg. by oral route, 345.2: 27.1 mg./kg. by intravenous route and 365:255 mg./ kg. by intraperitoneal route.
• the tris (hydroxymethyl) aminomethane theophylline. acetate can be considered, by its characteristics, as a complete antiacidotic product since it acts not only on the blood factors that regulate the pH but also on the cellular pulmonary and renal factors.
• the new compound acts as a proton acceptor neutralizing the intracellular hydrogen ions.
• respiratory acidosis the depressant action of tris (hydroxymethyl) aminomethane on the respiratory centers is counter acted by the stimulant action exerted by the theophylline on them.
• renal acidosis there is a synergism between the diuretic action of osmotic and tubular type of the tris (hydroxymethyl) aminomethane with that of glomerular type of the theophylline.
• the tris (hydroxymethyl) aminomethane theophylline-acetate is indicated in all types of toxic, respiratory or metabolic acidosis of tissular, pulmonary, plasmatic, or renal origin. Also in intoxications of medicamental origin produced by barbiturates, salicylic derivatives and the like, in which it facilitates the quick elimination of the toxic substances by renal route.
• the new compound can be administered, unlike the tris (hydroxymethyl) aminomethane, by oral route without producing digestive troubles, and by intravenous route without provoking irritations.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Engineering & Computer Science (AREA)
• Biochemistry (AREA)
• Biotechnology (AREA)
• General Health & Medical Sciences (AREA)
• Genetics & Genomics (AREA)
• Molecular Biology (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Applications Claiming Priority (1)

Publications (1)

Family

ID=8442738

Family Applications (1)

Country Status (7)

Cited By (17)

Families Citing this family (3)

• 1966
  • 1966-02-17 ES ES0323195A patent/ES323195A1/es not_active Expired
• 1967
  • 1967-02-15 GB GB7186/67A patent/GB1113600A/en not_active Expired
  • 1967-02-16 BE BE694127D patent/BE694127A/xx unknown
  • 1967-02-16 DE DE19671695358 patent/DE1695358A1/de active Pending
  • 1967-02-17 CH CH240367A patent/CH469659A/fr unknown
  • 1967-02-17 FR FR95468A patent/FR1511911A/fr not_active Expired
  • 1967-02-17 US US616780A patent/US3562273A/en not_active Expired - Lifetime

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