US3758684A - Treating dna virus infections with amino purine derivatives - Google Patents

Treating dna virus infections with amino purine derivatives Download PDF

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US3758684A
US3758684A US00178483A US3758684DA US3758684A US 3758684 A US3758684 A US 3758684A US 00178483 A US00178483 A US 00178483A US 3758684D A US3758684D A US 3758684DA US 3758684 A US3758684 A US 3758684A
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dna virus
pharmaceutically acceptable
purine
compound
arabinofuranosyl
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G Elion
R Strelitz
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Wellcome Foundation Ltd
SmithKline Beecham Corp
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Wellcome Foundation Ltd
Burroughs Wellcome Co USA
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/16Purine radicals

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  • ABSTRACT Compounds of the formula 1 N l m1 noon: ⁇ NAN (Fog 11" l 11 011? H on 11 where R is amino or lower alkylamino, R is amine or hydrogen and pharmaceutically acceptable salts thereof, provided that when R is amino, R is amino.
  • the compounds are useful as immune suppressants and as antivirals.
  • This invention relates to purine sugar derivatives which are useful as suppressors of the immune response and as antiviral agents. g I
  • the compounds of this invention are of the formula where R is amino or lower alkyl amino, R is amino or hydrogen, provided that whenever R is amino, R is amino.
  • lower alkyl is defined as having I to 4 carbon atoms (i.e. methyl, ethyl, propyl,,and butyl).
  • the compounds of this invention may also be provided as salts and be used in pharmacological and medical applications as pharmaceutically acceptable salts, although it should be understood that the activity of any salt administered or used medically resides in the base.
  • toxic salts can be made and converted to either the base or pharmaceutically acceptable salts by standard decomposition methods.
  • Salts which are especially preferred for therapeutic use are salts of pharmaceutically acceptable carboxylic acids such as lactic, acetic, malic as well as salts of pharmaceutically acceptable weak mineral acids.
  • the compounds of formula I and their pharmaceutically acceptable salts are particularly useful in treating viral infections resulting from DNA viruses, of which type vaccinia and herpes are examples.
  • the compounds of Formula I or their pharmaceuticallyacceptable salts would preferably be applied to the infected part of the body of the patient as atopical ointment.
  • the compounds of this invention are also useful in treating systemic vaccinial and herpes viral infections and for such use, the compounds are preferably administered orally or parenterally.
  • the compoundsof Formula I or theirpharmaceutically acceptable salts are also useful to suppress the immune response of an animal to the transplant of foreign cells into the body of the animal.
  • the compounds of Formula I or their pharmaceuticallyacceptable salts are also useful in the treatment of autoimmune diseases in mammals such as Lupus Erythematosis, Hemolytic anemia, Ulcerat-ive Colitis and Nephrosis.
  • the compounds of this invention are preferably used internally 9 (orally or parenterally) for the treatment of viral infections at dose levels (as base) at about l-IOO mg./kg. of mammal bodywei'ght, and is preferably used in man in a unit dosage form (administered a few times daily) in the amount of 10 to 250 mg. per unit dose depending on the patient being treated.
  • dose levels as base
  • unit dosage form administered a few times daily
  • the amount used would be about one half of that used for internal use. 4 I
  • the compounds of Formula I are administered internally at dosages preferrably of about 3 to 10 mg./kg. of mammal body weight.
  • the compound where R and R are both amino is the most preferred, particularly for its extremely high antiviral activity.
  • This compound, 2,6-diamino-9-(B-D- arabinofuranosyl) purine has in tests been found to be an extremely effective as an antiviral agent, as for example, against the herpes virus.
  • mice infected intracerebrally with I00 LB of herpes virus were injected subcutaneously with 1 mg. (50 mg./kg.)
  • 2,6-diamino-9-B-D-arabinofuranosyl) purine (twice daily to a total of five doses).
  • the injection is preferably a solution of the compound in a sterile fluid, i.e. water since the compound is readily soluble.
  • the compound 2 ,6-diamino-9-(B-D- arabinofuranosyl) purine has also shown substantial and unexpectedly high activity against vaccinia virus.
  • percent survival were achieved with the treated mice, while all the mice of the control group died within 4 6 days.
  • the compound2,6-diamino-9- (B-D-arabinofuranosyl) purine or its salts may be given parenterally (in an injectable solution), orally (tablets or'ca'psules), used as a suppository, applied as an optic solution, or applied topically as an ointment, cream, powder, etc., as a pharmaceutical preparation in accor dance with known medical or veterinarial practice.
  • the preferred compound is preferably administered at a dosage of about I to I00 mgJkg. -of mammal body weight (i.e/mice, rats, dogs, humans). In a unit dosage the compound is preferably administered at a dosage of about 10-250 mg.
  • the preferred drug or compound is preferably given orally and at a dose level of about 3to IO mg/kg. of mammal body weight a few times daily.
  • the compounds of Formula I may be conveniently prepared by reducing (i.e. by catalytic hydrogenation) the compound of Formula II.
  • Z is a blocking group such that when attached to the oxygen atom at position 2 of the sugar moiety, there is no interference with processes at carbon No. l of the sugar.
  • acyl is not acceptable as Z but alkyl is.
  • a further limitation is that Z should be removable, when desired, under mild conditions.
  • the benzyl group satisfies both requirements and is preferred. Others that can be used are p-phenylbenzyl and a and B-menaphthyl. The reduction may be accomplished catalytically, i.e.
  • hydrogenation catalyst such as palladium, palladized charcoal, platinum black, Raney nickel
  • a reducing agent such as sodium in liquid ammonia. Potassium and other alkali metals may also be used.
  • Step (c) The compound of Formula III where X and X are NH is then'further reduced in Step (c) catalytically or by using alkali metal (i.e. sodium) in liquid ammonia.
  • alkali metal i.e. sodium
  • steps (b) and (c) are reductive processes which can be combined into one step using either of the reductive methods described previously in the description for making the compounds of Formula I from the intermediates therefore.
  • compositions or preparations comprising a compound of For-' mula I or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier therefore.
  • the compositions may be used orally, parenterally, or topically depending on whether the preparation is used to treat internal or external viral infections caused by DNA viruses.
  • It is preferably administered orally or as a solution (injection) when it is an immune .or autoimmunal response suppressant.
  • DNA viruses are those viruses which utilize DNA as building blocks.
  • the invention also provides novel and .usefulcompounds of the above formulas.
  • fine powders or granules of the compounds may contain diluting, dispersing and/or surfaceactive agents, and may be presented ina draft, in water or ina syrup, in capsules or cachets in the dry state or in a non-aqueous suspension wherein suspending agents may be included; in tablets, when binders and lubricants may be included; or in a suspension in 1 water or a syrup.
  • flavouring,preserving, suspending, thickening or emulsifying agents can be included. Tablets and granules are preferred, and these may be coated.
  • parenteral administration the compounds may be presented in aqueous injection solutions which may contain antioxidants, bufiers etc.
  • the precipitated sodium chloride was filtered off, and the yellow filtrate,.containing the 2,6- diazido-9-(2,3,5-tri-0-benzyl-B-D-arabinofuranosyl). purine showed absorption maxima at 245,270 (shoulder), 300 mu in percent ethanol. The filtrate was used directly for the reduction in the next step.
  • a method of treating a mammal having a DNA virus infection which comprises administering to the infected mammal an effective DNA virus treatment amount of 2,6-diamino-9-(B-D-arabinofuranosyl) purine or a pharmaceutically acceptable salt thereof.
  • a pharmaceutical preparation in dosage unit form adapted for internal administration to obtain an anti DNA virus effect comprising per dosage unit, an anti DNA virus effective non-toxic amount within the range of 10 to 250 mg of 2,6-diamino-9-(B-D- arabinofuranosyl) purine or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
  • a pharmaceutical preparation in dosage unit form adapted for external administration to obtain an anti DNA virus effect comprising per dosage unit, an anti DNA virus effective non-toxic amount within the range of 5 to mg of 2,6-diamino-9-(B-D- arabinofuranosyl) purine or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

Abstract

Compounds of the formula

WHERE R1 is amino or lower alkylamino, R2 is amine or hydrogen and pharmaceutically acceptable salts thereof, provided that when R1 is amino, R2 is amino. The compounds are useful as immune suppressants and as antivirals.

Description

United States Patent 1191 Elion et a1.
[ TREATING DNA VIRUS INFECTIONS WITH AMINO PURINE DERIVATIVES [75] Inventors: Gertrude B. Elion, Bronxville, N.Y.;
Robert A. Strelitz, Edison, NJ.
[52] U.S. Cl. 424/180 [51] Int. Cl A6Ik 27/00 [58] Field of Search 424/180; 260/21 1.5
[56] References Cited UNITED STATES PATENTS 10/1969 Hanessian 260/2115 OTHER PUBLICATIONS Montgomery et al., J. Med. Chem., Vol. 12, May 1969, pages 498-504.
1 51 Sept. 11, 1973 Primary ExaminerRichard L. Huff Attorney-D0nald Brown et a1.
[57] ABSTRACT Compounds of the formula 1 N l m1 noon: \NAN (Fog 11" l 11 011? H on 11 where R is amino or lower alkylamino, R is amine or hydrogen and pharmaceutically acceptable salts thereof, provided that when R is amino, R is amino. The compounds are useful as immune suppressants and as antivirals.
5 Claims, No Drawings TREATING DNA VIRUS INFECTIONS WITH AMINO PURINE DERIVATIVES This is a division, of application Ser. No. 877,443, filed Nov. l7, I969.
This invention relates to purine sugar derivatives which are useful as suppressors of the immune response and as antiviral agents. g I
The compounds of this invention are of the formula where R is amino or lower alkyl amino, R is amino or hydrogen, provided that whenever R is amino, R is amino. g
In the above, lower alkyl is defined as having I to 4 carbon atoms (i.e. methyl, ethyl, propyl,,and butyl).
The compounds of this invention may also be provided as salts and be used in pharmacological and medical applications as pharmaceutically acceptable salts, although it should be understood that the activity of any salt administered or used medically resides in the base. In addition, toxic salts can be made and converted to either the base or pharmaceutically acceptable salts by standard decomposition methods.
Salts which are especially preferred for therapeutic use are salts of pharmaceutically acceptable carboxylic acids such as lactic, acetic, malic as well as salts of pharmaceutically acceptable weak mineral acids.
The compounds of formula I and their pharmaceutically acceptable salts are particularly useful in treating viral infections resulting from DNA viruses, of which type vaccinia and herpes are examples.
For viral infections of the eye or other external tissues such as caused-by the aboveviruses the compounds of Formula I or their pharmaceuticallyacceptable salts would preferably be applied to the infected part of the body of the patient as atopical ointment. The compounds of this invention are also useful in treating systemic vaccinial and herpes viral infections and for such use, the compounds are preferably administered orally or parenterally.
The compoundsof Formula I or theirpharmaceutically acceptable salts are also useful to suppress the immune response of an animal to the transplant of foreign cells into the body of the animal. The compounds of Formula I or their pharmaceuticallyacceptable salts are also useful in the treatment of autoimmune diseases in mammals such as Lupus Erythematosis, Hemolytic anemia, Ulcerat-ive Colitis and Nephrosis.
The compounds of this invention are preferably used internally 9 (orally or parenterally) for the treatment of viral infections at dose levels (as base) at about l-IOO mg./kg. of mammal bodywei'ght, and is preferably used in man in a unit dosage form (administered a few times daily) in the amount of 10 to 250 mg. per unit dose depending on the patient being treated. For use as an ointment, the amount used would be about one half of that used for internal use. 4 I
For use as immune supressants, the compounds of Formula I, are administered internally at dosages preferrably of about 3 to 10 mg./kg. of mammal body weight.
Of the compounds of Formula I, the compound where R and R are both amino, is the most preferred, particularly for its extremely high antiviral activity. This compound, 2,6-diamino-9-(B-D- arabinofuranosyl) purine has in tests been found to be an extremely effective as an antiviral agent, as for example, against the herpes virus. In particular, mice infected intracerebrally with I00 LB of herpes virus were injected subcutaneously with 1 mg. (50 mg./kg.)
2,6-diamino-9-B-D-arabinofuranosyl) purine (twice daily to a total of five doses). The injection is preferably a solution of the compound in a sterile fluid, i.e. water since the compound is readily soluble. After five doses, in comparison with five untreated controls, a hundred percent of the treated mice survived at least five days without clinical signs of infection, whereas 60 I percent of the controls died, and the two remaining controls were moribund after five days.
The compound 2 ,6-diamino-9-(B-D- arabinofuranosyl) purine has also shown substantial and unexpectedly high activity against vaccinia virus. Five mice injected intracerebrally with I00 LD of Vaccinia virus were given the compound subcutane= ously in a dose of l mg. (50 mg./kg.) twice a day. In comparison with 'a control group of five'injected but untreated mice, percent survival were achieved with the treated mice, while all the mice of the control group died within 4 6 days.
Experiments have also shown that the preferred compound of this invention 2,6-diamino-9-(B-D- arabinofuranosyl) purine is unexpectedly useful in suppressing the immune response to transplanted cells. We have been able to demonstrate the immunosuppresive activity of this preferred compound against antibodies generated upon the transplant of cells into mammals (i.e. mice).
i For use as an antiviral, the compound2,6-diamino-9- (B-D-arabinofuranosyl) purine or its salts may be given parenterally (in an injectable solution), orally (tablets or'ca'psules), used as a suppository, applied as an optic solution, or applied topically as an ointment, cream, powder, etc., as a pharmaceutical preparation in accor dance with known medical or veterinarial practice. The preferred compound is preferably administered at a dosage of about I to I00 mgJkg. -of mammal body weight (i.e/mice, rats, dogs, humans). In a unit dosage the compound is preferably administered at a dosage of about 10-250 mg. per unit dose which is preferably given or used a few (2-4) times daily. For external usage thedosage is preferably one half the dosage given above, i.e. S to 50 nag/kg. or 5'-l25 mg. per unitdose. For use in the treatment of autoimmune conditions or in immunosuppressive applications, the preferred drug or compound is preferably given orally and at a dose level of about 3to IO mg/kg. of mammal body weight a few times daily.
The compounds of Formula I may be conveniently prepared by reducing (i.e. by catalytic hydrogenation) the compound of Formula II.
where R and R is as defined previously above, to prepare the corresponding compound of formula I. Z is a blocking group such that when attached to the oxygen atom at position 2 of the sugar moiety, there is no interference with processes at carbon No. l of the sugar. For such purposes acyl is not acceptable as Z but alkyl is. A further limitation is that Z should be removable, when desired, under mild conditions. The benzyl group satisfies both requirements and is preferred. Others that can be used are p-phenylbenzyl and a and B-menaphthyl. The reduction may be accomplished catalytically, i.e. by use of hydrogenation catalyst such as palladium, palladized charcoal, platinum black, Raney nickel, or by reacting the compound of Formula II with a reducing agent such as sodium in liquid ammonia. Potassium and other alkali metals may also be used.
The preferred compound (R=R =NH of Formula I is preferably made by the following sequence of"steps. A compound of Formula III where X and X is halogen, preferably chlorine or bromine and Z is a blocking group as defined above, preferably benzylis reacted as follows: v
0 Z H I (III) I an alkali metal azide (preferably H II ' Compound of Formula III where X and X are NH, and where a portion (some of the end product) is the preferred compound of Formula I.
Step (c) The compound of Formula III where X and X are NH is then'further reduced in Step (c) catalytically or by using alkali metal (i.e. sodium) in liquid ammonia. In practice, steps (b) and (c) are reductive processes which can be combined into one step using either of the reductive methods described previously in the description for making the compounds of Formula I from the intermediates therefore.
Thus the present invention provides the above methods of preparation of the compound of Formula I and the preferred compound R and R =NH and acid addition salts thereof.
This invention also provides pharmaceutical compositions or preparations comprising a compound of For-' mula I or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier therefore. The compositions may be used orally, parenterally, or topically depending on whether the preparation is used to treat internal or external viral infections caused by DNA viruses.
It is preferably administered orally or as a solution (injection) when it is an immune .or autoimmunal response suppressant.
This invention also provides a method for treating viral infections caused by DNA viruses in mammals, (i.e. mice, rats, dogs, man etc.) by administering an effective non-toxic antiviral amount of a compound of Formula 1 (preferably where R'=R ==NH or a salt thereof to the infected mammal. DNA viruses are those viruses which utilize DNA as building blocks.
The invention also provides novel and .usefulcompounds of the above formulas.
For oral administration, fine powders or granules of the compounds may contain diluting, dispersing and/or surfaceactive agents, and may be presented ina draft, in water or ina syrup, in capsules or cachets in the dry state or in a non-aqueous suspension wherein suspending agents may be included; in tablets, when binders and lubricants may be included; or in a suspension in 1 water or a syrup.
Where desirable or necessary flavoring,preserving, suspending, thickening or emulsifying agents can be included. Tablets and granules are preferred, and these may be coated. For parenteral administration, the compounds may be presented in aqueous injection solutions which may contain antioxidants, bufiers etc.
The following examples illustrate the invention:
EXAMPLE I 2,6-Diazido-9-(2,3,S-tri-Obenzyl-B-D- arabinofuranosyl)purine(I) A solution of 2.1 g. of 2,6-dichloro-9-(2,3,S-tri-O- b'enzyl-fi D-a'rabinofuranoxyl)purine (Keller et al., J. Org. Chem., 32, 1644 [1967]) in 8 ml. of methanol and 2 vml. of acetone was heated with 440 mg. (2 molecular equivalents) of sodium azide for 6 hours under reflux conditions. The precipitated sodium chloride was filtered off, and the yellow filtrate,.containing the 2,6- diazido-9-(2,3,5-tri-0-benzyl-B-D-arabinofuranosyl). purine showed absorption maxima at 245,270 (shoulder), 300 mu in percent ethanol. The filtrate was used directly for the reduction in the next step.
EXAMPLE ll 2,6-Diamino-9-(2,3 ,S-tri-O-benzyl-B-D- arabinofuranosyl)purine(ll) g. of pale yellow crystals, m.p. l58l59, which was I homogeneous on thin-layer chromatography. The analysis corresponded to 2,6-diamino-9-(2,3,5-tri-0-benzyl- B-D-arabinofuranosyl)purine.
EXAMPLE Ill 2,6-Diamino-9-(B-D-arabinofuranosyl)purine To 1 g. of product I] was added 200 ml. of liquid ammonia. Small pieces of sodium were added until the blue color persisted for several minutes. A total of 350 mg. of sodium was used. The blue color was discharged with a few crystals of ammonium chloride. The ammonia was evaporated under a stream of nitrogen and the residue was triturated with 50 ml. of benzene. The insoluble residue was taken up in a few ml. of water and neutralized with acetic acid. The product (500 mg.), after recrystallization from water, melted at 257-259 with decomposition. The 2,6-diamino-9-(B-D- arabinofuranosyl)purine showed a Amax=253,290 mu at pH 1, and xmax=257, 279 mu at pH 11.
What is claimed is:
l. A method of treating a mammal having a DNA virus infection which comprises administering to the infected mammal an effective DNA virus treatment amount of 2,6-diamino-9-(B-D-arabinofuranosyl) purine or a pharmaceutically acceptable salt thereof.
2. A method according to claim 1 in which the amount is l to mg/kg of mammal bodyweight.
3. A method according to claim 1 in which the amount is 0.5 to 50 mg/kg of mammal bodyweight.
4. A pharmaceutical preparation in dosage unit form adapted for internal administration to obtain an anti DNA virus effect, comprising per dosage unit, an anti DNA virus effective non-toxic amount within the range of 10 to 250 mg of 2,6-diamino-9-(B-D- arabinofuranosyl) purine or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
5. A pharmaceutical preparation in dosage unit form adapted for external administration to obtain an anti DNA virus effect, comprising per dosage unit, an anti DNA virus effective non-toxic amount within the range of 5 to mg of 2,6-diamino-9-(B-D- arabinofuranosyl) purine or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

Claims (4)

  1. 2. A method according to claim 1 in which the amount is 1 to 100 mg/kg of mammal bodyweight.
  2. 3. A method according to claim 1 in which the amount is 0.5 to 50 mg/kg of mammal bodyweight.
  3. 4. A pharmaceutical preparation in dosage unit form adapted for internal administration to obtain an anti DNA virus effect, comprising per dosage unit, an anti DNA virus effective non-toxic amount within the range of 10 to 250 mg of 2,6-diamino-9-( Beta -D-arabinofuranosyl) purine or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
  4. 5. A pharmaceutical preparation in dosage unit form adapted for external administration to obtain an anti DNA virus effect, comprising per dosage unit, an anti DNA virus effective non-toxic amount within the range of 5 to 125 mg of 2,6-diamino-9-( Beta -D-arabinofuranosyl) purine or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
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* Cited by examiner, † Cited by third party
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US5292725A (en) * 1988-08-25 1994-03-08 Prendergast Patrick T Administering particular compounds against various parasites, mycoplasmas, other indications and other infections
US5308837A (en) * 1990-08-22 1994-05-03 Merrell Dow Pharmaceuticals Inc. 5'-amine substituted adenosine analogs as immunosuppressants
US5424295A (en) * 1987-05-30 1995-06-13 Burroughs Wellcome Co. 9-β-D-arabinofuranasyl-2-amino-6-methaoxy-9H-purine
US5681831A (en) * 1988-08-25 1997-10-28 Prendergast; Patrick T. Method of treating viral and retroviral infections including HIV by administration of N6 -(Δ)2 -isopentenyl) adenosine or an analogue thereof
US5681941A (en) * 1990-01-11 1997-10-28 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
US6232463B1 (en) 1997-10-09 2001-05-15 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
US8722743B2 (en) 2010-04-19 2014-05-13 Oryzon Genomics S.A. Lysine specific demethylase-1 inhibitors and their use
US8859555B2 (en) 2009-09-25 2014-10-14 Oryzon Genomics S.A. Lysine Specific Demethylase-1 inhibitors and their use
US8946296B2 (en) 2009-10-09 2015-02-03 Oryzon Genomics S.A. Substituted heteroaryl- and aryl-cyclopropylamine acetamides and their use
US8993808B2 (en) 2009-01-21 2015-03-31 Oryzon Genomics, S.A. Phenylcyclopropylamine derivatives and their medical use
US9006449B2 (en) 2010-07-29 2015-04-14 Oryzon Genomics, S.A. Cyclopropylamine derivatives useful as LSD1 inhibitors
US9061966B2 (en) 2010-10-08 2015-06-23 Oryzon Genomics S.A. Cyclopropylamine inhibitors of oxidases
US9181198B2 (en) 2010-07-29 2015-11-10 Oryzon Genomics S.A. Arylcyclopropylamine based demethylase inhibitors of LSD1 and their medical use
US9186337B2 (en) 2010-02-24 2015-11-17 Oryzon Genomics S.A. Lysine demethylase inhibitors for diseases and disorders associated with Hepadnaviridae
US9469597B2 (en) 2011-10-20 2016-10-18 Oryzon Genomics S.A. (Hetero)aryl cyclopropylamine compounds as LSD1 inhibitors
US9487512B2 (en) 2011-10-20 2016-11-08 Oryzon Genomics S.A. (Hetero)aryl cyclopropylamine compounds as LSD1 inhibitors
US9616058B2 (en) 2010-02-24 2017-04-11 Oryzon Genomics, S.A. Potent selective LSD1 inhibitors and dual LSD1/MAO-B inhibitors for antiviral use
US9790196B2 (en) 2010-11-30 2017-10-17 Oryzon Genomics S.A. Lysine demethylase inhibitors for diseases and disorders associated with Flaviviridae

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* Cited by examiner, † Cited by third party
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US5424295A (en) * 1987-05-30 1995-06-13 Burroughs Wellcome Co. 9-β-D-arabinofuranasyl-2-amino-6-methaoxy-9H-purine
US5292725A (en) * 1988-08-25 1994-03-08 Prendergast Patrick T Administering particular compounds against various parasites, mycoplasmas, other indications and other infections
US5681831A (en) * 1988-08-25 1997-10-28 Prendergast; Patrick T. Method of treating viral and retroviral infections including HIV by administration of N6 -(Δ)2 -isopentenyl) adenosine or an analogue thereof
US5681941A (en) * 1990-01-11 1997-10-28 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
US5308837A (en) * 1990-08-22 1994-05-03 Merrell Dow Pharmaceuticals Inc. 5'-amine substituted adenosine analogs as immunosuppressants
US5811534A (en) * 1994-02-01 1998-09-22 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
US6232463B1 (en) 1997-10-09 2001-05-15 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
US8993808B2 (en) 2009-01-21 2015-03-31 Oryzon Genomics, S.A. Phenylcyclopropylamine derivatives and their medical use
US8859555B2 (en) 2009-09-25 2014-10-14 Oryzon Genomics S.A. Lysine Specific Demethylase-1 inhibitors and their use
US8946296B2 (en) 2009-10-09 2015-02-03 Oryzon Genomics S.A. Substituted heteroaryl- and aryl-cyclopropylamine acetamides and their use
US9616058B2 (en) 2010-02-24 2017-04-11 Oryzon Genomics, S.A. Potent selective LSD1 inhibitors and dual LSD1/MAO-B inhibitors for antiviral use
US9186337B2 (en) 2010-02-24 2015-11-17 Oryzon Genomics S.A. Lysine demethylase inhibitors for diseases and disorders associated with Hepadnaviridae
US8722743B2 (en) 2010-04-19 2014-05-13 Oryzon Genomics S.A. Lysine specific demethylase-1 inhibitors and their use
US10202330B2 (en) 2010-04-19 2019-02-12 Oryzon Genomics, Sa Lysine specific demethylase-1 inhibitors and their use
US9149447B2 (en) 2010-04-19 2015-10-06 Oryzon Genomics S.A. Lysine specific demethylase-1 inhibitors and their use
US9181198B2 (en) 2010-07-29 2015-11-10 Oryzon Genomics S.A. Arylcyclopropylamine based demethylase inhibitors of LSD1 and their medical use
US9676701B2 (en) 2010-07-29 2017-06-13 Oryzon Genomics, S.A. Cyclopropylamine derivatives useful as LSD1 inhibitors
US9708309B2 (en) 2010-07-29 2017-07-18 Oryzon Genomics, S.A. Arylcyclopropylamine based demethylase inhibitors of LSD1 and their medical use
US9006449B2 (en) 2010-07-29 2015-04-14 Oryzon Genomics, S.A. Cyclopropylamine derivatives useful as LSD1 inhibitors
US10233178B2 (en) 2010-07-29 2019-03-19 Oryzon Genomics, S.A. Arylcyclopropylamine based demethylase inhibitors of LSD1 and their medical use
US9061966B2 (en) 2010-10-08 2015-06-23 Oryzon Genomics S.A. Cyclopropylamine inhibitors of oxidases
US9790196B2 (en) 2010-11-30 2017-10-17 Oryzon Genomics S.A. Lysine demethylase inhibitors for diseases and disorders associated with Flaviviridae
US9469597B2 (en) 2011-10-20 2016-10-18 Oryzon Genomics S.A. (Hetero)aryl cyclopropylamine compounds as LSD1 inhibitors
US9487512B2 (en) 2011-10-20 2016-11-08 Oryzon Genomics S.A. (Hetero)aryl cyclopropylamine compounds as LSD1 inhibitors
US9670136B2 (en) 2011-10-20 2017-06-06 Oryzon Genomics S.A. (Hetero)aryl cyclopropylamine compounds as LSD1 inhibitors
US9944601B2 (en) 2011-10-20 2018-04-17 Oryzon Genomics, S.A. (Hetero)aryl cyclopropylamine compounds as LSD1 inhibitors
US10214477B2 (en) 2011-10-20 2019-02-26 Oryzon Genomics S.A. (Hetero)aryl cyclopropylamine compounds as LSD1 inhibitors
US10329256B2 (en) 2011-10-20 2019-06-25 Oryzon Genomics, S.A. (Hetero)aryl cyclopropylamine compounds as LSD1 inhibitors

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