Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1998-09-11
2000-11-07
Elliott, George C.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
424 121, 424 145, 424 9321, 424 932, 424417, 424450, 435325, 264 41, 264 43, 935 52, 935 54, A61K 4800, A61K 3170, A61K 5100, C12N 500, B01J 1302, B01J 1304
Patent
active
061437298
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to new compounds related to the amidinium family, including in particular the guanidiniums, pharmaceutical compositions containing them and their applications.
More precisely, the present invention relates to compounds of general formula I and their salts ##STR2## in which: R1 represents a cholesterol derivative or an alkylamino --NR'R" group with R' and R" representing, independently of each other, a saturated or unsaturated, linear or branched C.sub.12 to C.sub.22 aliphatic radical, group of general formula II with at least one of them being different from a hydrogen atom, ##STR3## in which n and m represent, independently of each other and distinctly between the groups R2 and R3, an integer between 0 and 4, group of formula III ##STR4## in which p and q represent, independently of each other, an integer between 0 and 4 and r is equal to 0 or 1, with r equal to 1 R4 and R5.
By way of preferred subfamily, there may be mentioned more particularly within the framework of the present invention the compounds of general formula I in which R2 or R3 represent, independently of each other, a hydrogen atom or a group of formula IV ##STR5## in which n, m and p are as defined above and R4 represents a hydrogen atom or a group of formula V ##STR6## with q and r as defined above, and it being possible for m, n, p, q and r to vary independently between the different groups R2 and R3.
These new products of general formula (I) may be provided in the form of nontoxic and pharmaceutically acceptable salts. These nontoxic salts comprise the salts with inorganic acid (hydrochloric, sulphuric, hydrobromic, phosphoric or nitric acids) or with organic acids (acetic, propionic, succinic, maleic, hydroxymaleic, benzoic, fumaric, methane-sulphonic or oxalic acids) or with inorganic bases (sodium hydroxide, potassium hydroxide, lithium hydroxide or calcium hydroxide) or organic bases (tertiary amines such as triethylamine, piperidine or benzylamine).
As representatives of the compounds according to the invention, there may be mentioned more particularly the compounds of the following general subformulae: C.sup.+ --NH--(CH.sub.2).sub.4 ]--N--COO--R1 VII --N--(CH.sub.2).sub.2 --NH--COO--R1 VIII ].sub.2 N--COO--R1 X
As representatives of the claimed guanidiniums and amidiniums, there may be mentioned more particularly the compounds of the above subformulae VII, VIII and IX with R1 representing therein a cholesteryl group. The three compounds will be respectively identified hereinafter by the name BGSC (Bis Guanidino Spermidine Cholesterol) and BGTC (Bis Guanidino Tren Cholesterol) and BADC (Bis Amidinium Diethylenetriamine Cholesterol bishydrochloride).
The claimed compounds are most particularly advantageous from the therapeutic point of view for their nontoxic characteristics and their amphiphilic properties. Given these qualities, they may in particular be used for complexing nucleic acids in the perspective of cellular transfection thereof. These compounds may therefore be advantageously used in gene therapy.
Compounds VII (BGSC) and VIII (BGTC) are most particularly advantageous for in vivo gene transfer. These two compounds form a complex with DNA and protect it against degradation due to pH variations during transport to the cell to be treated.
The invention therefore relates to a pharmaceutical composition which comprises at least one compound according to the invention. In a preferred embodiment of the invention, the compound is Bis Guanidino Spermidine Cholesterol (BGSC) and in another preferred embodiment, the compound is Bis Guanidino Tren Cholesterol (BGTC).
The principal objective of gene therapy is to correct genetic diseases associated with a defect in expression and/or an abnormal, that is to say a deficient or excessive, expression of one or more nucleic acids. Efforts are being made to correct this type of genetic abnormality through cellular expression in vivo or in vitro of cloned genes.
Nowadays, several methods are proposed for the intracellular delivery of this type of genetic info
REFERENCES:
patent: 5811406 (1998-09-01), Szoka et al.
Jayaraman et al., Approaches to Enhance the Binding Affinity and Nuclease Stability of Triplex Forming Oligonucleotides, Nucleosides & Nucleotides, vol. 14, Nos. 3-5, pp. 951-955 (1995).
Gagner, Liposome-mediated gene delivery--II. In vitro toxicity of cationic liposome DNA plasmid complexes, Chemical Abstracts, vol. 122, No. 11, p. 89 (1995) Abst. No. 123040.
Guy-Caffey et al., Novel Polyaminolipids Enhance the Cellular Uptake of Oligonucleotides, The Journal of Biol. Chem. vol. 270, No. 52, pp. 31391-31396 (1995).
Vigneron et al., Guanidinium-cholesterol cationic lipids: Efficient vectors for the transfection of eukaryotic cells, Proc. Natl. Acad. Sci. USA, vol. 93, pp. 9682-9686, Sep. 1996.
Lehn Jean-Marie
Lehn Pierre
Vigneron Jean-Pierre
Aventis Pharma S.A.
Elliott George C.
Epps Janet
LandOfFree
Compounds related to the amidinium family, pharmaceutical compos does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Compounds related to the amidinium family, pharmaceutical compos, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compounds related to the amidinium family, pharmaceutical compos will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1641195