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WO2003059352B1 - Use of a novel class of drugs for the treatment of parasitic diseases - Google Patents

Use of a novel class of drugs for the treatment of parasitic diseases

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Publication number
WO2003059352B1
WO2003059352B1 PCT/FR2003/000107 FR0300107W WO03059352B1 WO 2003059352 B1 WO2003059352 B1 WO 2003059352B1 FR 0300107 W FR0300107 W FR 0300107W WO 03059352 B1 WO03059352 B1 WO 03059352B1
Authority
WO
WIPO (PCT)
Prior art keywords
use according
hydrogen atom
alkyl chain
nrr
nhr
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/FR2003/000107
Other languages
French (fr)
Other versions
WO2003059352A3 (en
WO2003059352A2 (en
Inventor
Stanislas Tomavo
Florence Dzierszinski
Alexandra Coppin
Bels Frederic De
Jean-Claude Ameisen
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Centre National de la Recherche Scientifique CNRS
Original Assignee
Centre National de la Recherche Scientifique CNRS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Centre National de la Recherche Scientifique CNRS filed Critical Centre National de la Recherche Scientifique CNRS
Priority to AU2003214317A priority Critical patent/AU2003214317A1/en
Publication of WO2003059352A2 publication Critical patent/WO2003059352A2/en
Publication of WO2003059352A3 publication Critical patent/WO2003059352A3/en
Publication of WO2003059352B1 publication Critical patent/WO2003059352B1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A61P33/06—Antimalarials
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

The invention relates to the use of at least one ligand molecule of the peripheral benzodiazepine receptor (PBR) for the production of drugs that are intended for the treatment of parasitic diseases.

Claims

REVENDICATIONS MODIFIEES reçues par le Bureau international le 30 septembre 2003 (30.09.03); revendications 1-13 remplacées par les nouvelles revendications1-13 (5 pages).Revendications AMENDED CLAIMS received by the International Bureau on 30 September 2003 (30.09.03); Claims 1-13 replaced by the new claims1-13 (5 pages) .Reviews 1 . Utilisation d' au moins un composé de formule ( I) :1. Use of at least one compound of formula (I):
Figure imgf000002_0001
où X est un atome d'halogène choisi parmi F, Cl, Br ou I, un atome d'hydrogène, OH, COOH, SH, NH2, OR, COOR, SR, NHR ou NRR', où R et R' identiques ou différents, représentent une chaîne alkyle de 1, à 4 C,
Figure imgf000002_0001
where X is a halogen atom selected from F, Cl, Br or I, a hydrogen atom, OH, COOH, SH, NH 2 , OR, COOR, SR, NHR or NRR ', where R and R' are identical or different, represent an alkyl chain of 1 to 4 C, Ri efst un atome d'hydrogène, une chaîne alkyle de 1 à 4 C ou forme avec R4 une liaison de type C-N,Ri is a hydrogen atom, an alkyl chain of 1 to 4 C or form with R 4 a CN type bond, R2 est un atome d'hydrogène ou une chaîne hydrocarbonée de 1 à 6 C, comportant le cas échéant un groupement NHR ou NRR1, où R et R1 identiques ou différents, représentent une chaîne alkyle de 1 à 4 C,R 2 is a hydrogen atom or a hydrocarbon chain of 1 to 6 C, optionally comprising an NHR or NRR 1 group , in which R and R 1, which may be identical or different, represent an alkyl chain of 1 to 4 C, R3 est un atome d'hydrogène ou une chaîne hydrocarbonée de 1 à 2 C formant un cycle avec R ,R 3 is a hydrogen atom or a hydrocarbon chain of 1 to 2 C forming a ring with R, R4 forme avec R_ une liaison C-N, une chaîne hydrocarbonée de 1 à 2 C formant un cycle avec R3 ou un atome d'hydrogène.R 4 forms with R 1 a CN bond, a hydrocarbon chain of 1 to 2 C forming a ring with R 3 or a hydrogen atom. pour la fabrication de médicaments destinés au traitement de maladies parasitaires dues à des agents pathogènes de la famille des Api compl exa .for the manufacture of medicaments for the treatment of parasitic diseases caused by pathogens of the family Api compl exa. 2. Utilisation selon la revendication 1, caractérisée en ce que lesdites molécules sont des composés de formule (II) : 2. Use according to claim 1, characterized in that said molecules are compounds of formula (II):
Figure imgf000003_0001
où X est un atome d'halogène choisi parmi F, Cl, Br ou I, un atome d'hydrogène, OH, COOH, SH, NH2, OR, COOR, SR, NHR ou NRR', où R et R' identiques ou différents, représentent une chaîne alkyle de 1 à 4 C,
Figure imgf000003_0001
where X is a halogen atom selected from F, Cl, Br or I, a hydrogen atom, OH, COOH, SH, NH 2 , OR, COOR, SR, NHR or NRR ', where R and R' are identical or different, represent an alkyl chain of 1 to 4 C, Rx est un atome d'hydrogène, une chaîne alkyle de 1 à 4 C, R2 est un atome d'hydrogène ou une chaîne hydrocarbonée de 1 à 6 C, comportant le cas échéant un groupement NHR ou NRR' , où R et R' identiques ou différents, représentent une chaîne alkyle de 1 à 4 C.R x is a hydrogen atom, an alkyl chain of 1 to 4 C, R 2 is a hydrogen atom or a hydrocarbon chain of 1 to 6 C, optionally comprising an NHR or NRR 'group, where R and R 'identical or different, represent an alkyl chain of 1 to 4 C. 3. Utilisation selon la revendication 2, caractérisée en ce que le composé répond à la formule (IV) :3. Use according to claim 2, characterized in that the compound corresponds to formula (IV):
Figure imgf000003_0002
Figure imgf000003_0002
 4. Utilisation selon la revendication 1, caractérisée en ce que le composé répond à la formule (III) :4. Use according to claim 1, characterized in that the compound corresponds to formula (III):
Figure imgf000004_0001
ou X est un atome d'halogène choisi parmi F, Cl, Br ou I, un atome d'hydrogène, OH, COOH, SH, NH2, OR, COOR, SR, NHR ou NRR', où R et R' identiques ou différents, représentent une chaîne alkyle de 1 à 4 C,
Figure imgf000004_0001
or X is a halogen atom selected from F, Cl, Br or I, a hydrogen atom, OH, COOH, SH, NH 2 , OR, COOR, SR, NHR or NRR ', where R and R' are identical or different, represent an alkyl chain of 1 to 4 C, R2 est un atome d'hydrogène ou une chaîne hydrocarbonée de 1 à 6 C, comportant le cas échéant un groupement NHR ou NRR' , où R et R' identiques ou différents, représentent une chaîne alkyle de 1 à 4 C.R 2 is a hydrogen atom or a hydrocarbon chain of 1 to 6 C, optionally comprising an NHR or NRR 'group, in which R and R', which may be identical or different, represent an alkyl chain of 1 to 4C. 5. Utilisation selon la revendication 4, caractérisée en ce que le composé répond à la formule (V) :5. Use according to claim 4, characterized in that the compound corresponds to formula (V):
Figure imgf000004_0002
Figure imgf000004_0002
 6. Utilisation selon l'une quelconque des revendications précédentes, caractérisée en ce que les agents pathogènes sont Toxoplasma et Plasmodium, en particulier Toxoplasma gondii et Plasmodium Falciparu .6. Use according to any one of the preceding claims, characterized in that the pathogens are Toxoplasma and Plasmodium, in particular Toxoplasma gondii and Plasmodium Falciparu. 7. Utilisation selon l'une quelconque des revendications précédentes, caractérisée en ce que les médicaments présentent un effet inhibiteur dose dépendant vis-à vis du (des) parasite (s) .7. Use according to any one of the preceding claims, characterized in that the drugs have a dose-dependent inhibitory effect vis-à-vis the parasite (s). 8. Utilisation selon l'une quelconque des revendications précédentes, caractérisée en ce que les médicaments sont utilisés en multithérapie, conjointement et/ou en compléments de drogues anti- parasitaires, de préférence la chloroquine et/ou la méfloquine.8. Use according to any one of the preceding claims, characterized in that the drugs are used in combination therapy, jointly and / or in supplements of anti-parasitic drugs, preferably chloroquine and / or mefloquine. 9. Utilisation selon la revendication 2 ou 3 , caractérisée en ce que le composé est actif sur des souches de Plasmodium multi-résistantes aux médicaments, en particulier la souche Dd2 de Plasmodium falciparum.9. Use according to claim 2 or 3, characterized in that the compound is active on multi-drug resistant Plasmodium strains, in particular the strain Dd2 Plasmodium falciparum. 10. Utilisation selon la revendication 4 ou 5, caractérisée en ce que le composé est actif sur tous les stades parasitaires de Plasmodium falciparum.10. Use according to claim 4 or 5, characterized in that the compound is active on all parasitic stages of Plasmodium falciparum. 11. Utilisation selon l'une quelconque des revendications précédentes, caractérisée en ce que le médicament est formulé de manière à permettre une administration orale ou intraveineuse .11. Use according to any one of the preceding claims, characterized in that the drug is formulated to allow oral or intravenous administration. 12. Utilisation selon l'une quelconque des revendications précédentes caractérisée en ce que les doses administrées par voie orale sont comprises entre 10 μg et 0,5 mg/kg. 12. Use according to any one of the preceding claims, characterized in that the doses administered orally are between 10 micrograms and 0.5 mg / kg. 13. Test d'inhibition de l'activité anti-parasitaire, caractérisé en ce qu' il comporte les étapes suivantes : incubation des cellules avec des concentrations variables de parasites et/ou d'inhibiteurs à tester, - puis, mise en contact du milieu incubé avec les molécules telles qu'utilisées dans l'une quelconque des revendications 1 13. Inhibition test of the anti-parasitic activity, characterized in that it comprises the following steps: incubation of the cells with varying concentrations of parasites and / or inhibitors to be tested, - then, bringing into contact the medium incubated with the molecules as used in any one of claims 1
PCT/FR2003/000107 2002-01-15 2003-01-14 Use of a novel class of drugs for the treatment of parasitic diseases Ceased WO2003059352A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003214317A AU2003214317A1 (en) 2002-01-15 2003-01-14 Use of a novel class of drugs for the treatment of parasitic diseases

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR02/00439 2002-01-15
FR0200439A FR2834637A1 (en) 2002-01-15 2002-01-15 USE OF A NEW CLASS OF MEDICAMENTS FOR THE TREATMENT OF PARASITIC DISEASES

Publications (3)

Publication Number Publication Date
WO2003059352A2 WO2003059352A2 (en) 2003-07-24
WO2003059352A3 WO2003059352A3 (en) 2004-03-11
WO2003059352B1 true WO2003059352B1 (en) 2004-04-15

Family

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Family Applications (1)

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Country Status (3)

Country Link
AU (1) AU2003214317A1 (en)
FR (1) FR2834637A1 (en)
WO (1) WO2003059352A2 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2894478B1 (en) * 2005-12-08 2008-06-06 Anticiper Et Developper L Inno APPLICATION OF ISOQUINOLINE CARBOXAMIDE AND ITS DERIVATIVES AS BACTERIAL VIRULENCE INHIBITORS AS REPLACEMENT OR COMPLEMENT TO CLASSIC ANTIBIOTICS
WO2007088528A1 (en) * 2006-02-03 2007-08-09 The Provost, Fellows And Scholars Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth, Near Dublin Microtubule targeting agents
GB0907284D0 (en) 2009-04-28 2009-06-10 Queen Mary & Westfield College Compounds for inducing cellular apoptosis

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH602672A5 (en) * 1974-06-28 1978-07-31 Hoffmann La Roche
US5182387A (en) * 1991-10-30 1993-01-26 Merrell Dow Pharmaceuticals Inc. Bis-dibenzoazepine compounds
WO2001051922A2 (en) * 2000-01-14 2001-07-19 Mitokor Identification of peripheral benzodiazepine receptor binding agents

Also Published As

Publication number Publication date
FR2834637A1 (en) 2003-07-18
AU2003214317A1 (en) 2003-07-30
WO2003059352A3 (en) 2004-03-11
WO2003059352A2 (en) 2003-07-24

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