Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
  • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
  • C07H15/02—Acyclic radicals, not substituted by cyclic structures
  • C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical
• • 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
  • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
  • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P37/00—Drugs for immunological or allergic disorders
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P37/00—Drugs for immunological or allergic disorders
  • A61P37/02—Immunomodulators
  • A61P37/04—Immunostimulants

Definitions

• adjuvants impart synthetic peptide and carbohydrate antigens with sufficient immunogenicity to insure the success of the synthetic vaccine approach. There remains a need for new compounds having potent immunomodulating effects.
• the compounds of the subject invention are aminoalkyl glucosamine phosphate compounds (AGPs) which are adjuvants and immunoeffectors.
• AGPs aminoalkyl glucosamine phosphate compounds
• An aminoalkyl (aglycon) group is glycosidically linked to a 2-deoxy-2-amino- ⁇ -D-glucopyranose (glucosamine) to form the basic structure of the claimed molecules.
• the compounds are phosphorylated at the 4 or 6 carbon on the glucosamine ring. Further, the compounds possess three 3- alkanoyloxyalkanoyl residues.
• the number of carbon atoms between heteroatom X and the aglycon nitrogen atom is determined by variables "n” and "m". Variables "n” and “m” can be integers from 0 to 6. In a preferred embodiment, the total number of carbon atoms between heteroatom X and the aglycon nitrogen atom is from about 2 to about 6 and most preferably from about 2 to about 4.
• Another acceptable carrier includes 10%> USP ethanol and USP Water for Injection; yet another acceptable carrier is 0.01-0.1%) triethanolamine in USP Water for Injection.
• Pharmaceutically acceptable parenteral solvents are such as to provide a solution or dispersion may be filtered through a 5 micron filter without removing the active ingredient. Examples of carriers for administration via mucosal surfaces depend upon the particular route. When administered orally, pharmaceutical grades of mannitol, starch, lactose, magnesium stearate, sodium saccharide, cellulose, magnesium carbonate and the like, with mannitol being preferred.
• the compounds of the subject invention are synthesized by coupling an N- acyloxyacylated or N-protected aminoalkanol or aminoalkanethiol (aglycon unit) with a suitably protected and/or 3-O-acyloxyacylated glucosamine unit.
• Example 4-(3) the compound prepared in Example 4-(l) (3J g, 5.9 mmol) and (i?)-3-(allyloxycarbonylamino)-4- benzyloxy- 1 -butanol (1 J g, 3.94 mmol) were coupled in the presence of boron trifluoride etherate (3.0 mL, 23.6 mmol) to afford 1.96 g (67 %) of 4-benzyloxy-(S)-3- (allyloxycarbonylamino)butyl 2 -de oxy- 3 ,4,6 -tri-O-acety 1-2 -(2,2,2 - trichloroethoxycarbonylamino)- ⁇ -D-glucopyranoside as an amorphous solid.
• Example 2-(l) In the same manner as described in Example 2-(2), the compound prepared in Example 2-(l) (1.0 g, 2.02 mmol) was acylated with (R)-3- decanoyloxytetradecanoic acid (884 mg, 2.22 mmol) in the presence of EDC Mel (720 mg, 2.4 mmol) and 4-pyrrolidino ⁇ yridine (100 mg) in CH 2 C1 2 , and then deprotected in aqueous AcOH (25 mL) to afford 1.30g (77 %) of 2-(trimethylsilyl)ethyl 2-deoxy-3-O- [(i?)-3-decanoyloxytetradecanoyl]-2-(2,2,2-trichloroethoxycarbonylamino)- ⁇ -D- glucopyranoside as an amo ⁇ hous solid: 'H ⁇ MR (CDC1 3 ) ⁇ 0.00 (s, 9 H), 0.88 (m, 8
• Example 2-(l) In the same manner as described in Example 2-(2), the compound prepared in Example 2-(l) (1.0 g, 2.02 mmol) was acylated with (R)-3- octanoyloxytetradecanoic acid (821 mg, 2.22 mmol) in the presence of EDC Mel (720 mg, 2.4 mmol) and 4-pyrrolidinopyridine (100 mg) in CH 2 C1 2 , and then deprotected in 90 % aqueous AcOH (25 mL) to afford 1.35g (83 %) of 2-(trimethylsilyl)ethyl 2-deoxy-
• N-(2- hydroxyethyl)glycine t-butyl ester (0.25 g, 1.43 mmol) was acylated with (R)-3- tetradecanoyloxytetradecanoic acid (0.714 g, 1.57 mmol) in the presence of EDC-Mel (0.466 g, 1.57 mmol) to give 0.46 g (51%) of N-(2-hydroxyethyl)-N-[(i?)-3- tetradecanoyloxytetradecanoyl]glycine t-butyl ester as an amo ⁇ hous solid: 'H ⁇ MR
• R 8 P ⁇ 3 H 2 ).

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• Chemical & Material Sciences (AREA)
• Health & Medical Sciences (AREA)
• Organic Chemistry (AREA)
• Life Sciences & Earth Sciences (AREA)
• General Health & Medical Sciences (AREA)
• Engineering & Computer Science (AREA)
• Immunology (AREA)
• Molecular Biology (AREA)
• Biotechnology (AREA)
• Biochemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Medicinal Chemistry (AREA)
• Animal Behavior & Ethology (AREA)
• Genetics & Genomics (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Crystallography & Structural Chemistry (AREA)
• General Chemical & Material Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Epidemiology (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
• Medicinal Preparation (AREA)
• Cosmetics (AREA)
• Saccharide Compounds (AREA)

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Cited By (126)

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• 1997
  • 1997-05-08 US US08/853,826 patent/US6113918A/en not_active Expired - Lifetime
• 1998
  • 1998-05-07 AU AU74747/98A patent/AU740663B2/en not_active Expired
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  • 1998-05-07 WO PCT/US1998/009385 patent/WO1998050399A1/en not_active Ceased
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• 1999
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• 2009
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