EP1729765A1 - Use of a pyrazole derivative for producing medicaments that are useful in preventing and treating chronic bronchitis and chronic obstructive bronchopneumopathy - Google Patents

Use of a pyrazole derivative for producing medicaments that are useful in preventing and treating chronic bronchitis and chronic obstructive bronchopneumopathy

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Publication number
EP1729765A1
EP1729765A1 EP05739605A EP05739605A EP1729765A1 EP 1729765 A1 EP1729765 A1 EP 1729765A1 EP 05739605 A EP05739605 A EP 05739605A EP 05739605 A EP05739605 A EP 05739605A EP 1729765 A1 EP1729765 A1 EP 1729765A1
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EP
European Patent Office
Prior art keywords
useful
preventing
chronic obstructive
cannabinoid
pyrazole derivative
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.)
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Application number
EP05739605A
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German (de)
French (fr)
Inventor
Marie Sebille
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Sanofi Aventis France
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Sanofi Aventis France
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Publication of EP1729765A1 publication Critical patent/EP1729765A1/en
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    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/08—Bronchodilators

Definitions

  • the object of the present invention is the use of a cannabinoid CBj receptor antagonist compound, derived from pyrazole, for the preparation of medicaments useful in the prevention and treatment of chronic bronchitis and chronic obstructive pulmonary disease ( COPD, COPD: from English chronic obstructive pulmonary disease).
  • COPD chronic obstructive pulmonary disease
  • Endogenous cannabinoids such as anandamide, produce profound inhibition of coughing and contraction of the bronchial muscle. It has been observed that smoked cannabis shows broncho-dilating activity and it is known to use cannabinoid receptor agonists to treat various pathologies including bronchial asthma (Tashkin DP, Shapiro BJ, Lee YE, Harper EC:
  • CB ⁇ cannabinoid receptors by SR 141716A has no bronchomotor consequences per se but significantly increases the bronchoconstriction and cough caused by the administration of capsaicin.
  • Blockade of CB ⁇ cannabinoid receptors by SR 141716A inhibits the anti-inflammatory effect of two cannabinoid agonists HU210 and WLN 55212-2 produced on the migration of neutrophils in a peritonitis model in mice (Smith SR, Denhardt G, Terminelli C: The anti-inflammatory activities of cannabinoid receptor ligands in mouse peritonitis models, EUT. J. Pharmacol. 2001, 432: 107-119).
  • the CB receptor antagonists derived from pyrazole are active at the bronchopulmonary level and can be used in the treatment of chronic bronchitis.
  • the term “cannabinoid receptor antagonist derived from pyrazole” means N-piperidino-5- (4-chlorophenyl) -l- 2,4- dichlorophenyl) -4-methylpyrazole-3-carboxamide known by the name SR141716 and whose international common name is rimonabant described in European patent 656354, and N-piperidino-5- (4-bromophény ⁇ ) -l-C2,4- dichlorophenyl) -4-ethylpyrazole-3-carboxamide described in European patent 1150961. Clinical studies carried out with rimonabant have shown that it reduces the hunger, the caloric intake and the body weight of obese patients (G. Le Fur, 2003, 35, First European Workshop on Cannabinoi
  • a compound which is a CBj cannabinoid receptor antagonist, derived from pyrazole can be used for the preparation of medicaments useful for preventing and treating chronic bronchialitis and chronic obstructive pulmonary disease as well as the associated chronic brown hite. to chronic pulmonary bronchopneumopathy.
  • the pharmaceutical compositions according to the present invention contain an effective dose of a cannabinoid CB receptor antagonist compound, derived from pyrazole, as well as at least one pharmaceutically acceptable excipient. Said excipients are chosen according to the pharmaceutical form and the nxode of administration desired, from the usual excipients which are known to those skilled in the art.
  • the active principle can be administered in unit administration form , in admixture with conventional pharmaceutical excipients, to animals and humans for the prevention or treatment of the above disorders or diseases.
  • Suitable unit dosage forms include oral forms such as tablets, soft or hard capsules, powders, granules and oral solutions or suspensions, sublingual, buccal, intratracheal, intraocular, intranasal, inhalation administration forms, topical, transdermal, subcutaneous, intramuscular or intravenous administration forms, rectal administration forms and implants.
  • EXAMPLE 1 animal model Migration of cells into the bronchoalveolar space after activation by bacterial E PS (lipopolysaccharide). 28 to 30 g mice are stimulated by an intratracheal exposure of 10> ⁇ g of LPS. 24 hours after the LPS injection, the animals are anesthetized with pentobarbital and a bronchoalveolar lavage is carried out. The washing fluids are recovered, centrifuged and then the cells are resuspended.
  • E PS lipopolysaccharide
  • the number of cells is counted by differentiating, according to standard morphological criteria, the eosinophilic, neutrophilic and mononuclear cells.
  • Intratracheal injection of LPS induces a significant increase in the number of mononuclear and neutrophil cells in the bronchoalveolar space of mice.
  • Rimonabant is administered to animals 1 hour before LPS in doses varying from 0.3 to 30 mg / kg / ip
  • the effective dose 50 (ED 50 ) which inhibits the migration of neutrophil cells by more than 80% is 2.3 (+ 0.3) mg / kg.
  • ED 50 1.9 (+ 0.5) mg / kg.
  • This model induced by bacterial LPS is conventionally used, in particular in the bronchopulmonary level, where it produces an infiltration of polymorphonuclear neutrophil cells into the bronchopulmonary tissues followed by a release, of mediators which cause tissue damage.
  • This neutrophil infiltration is the consequence of the activation of mononuclear cells (macrophages which constitute the first defense barrier at the level of the bronchial epithelium and T lymphocytes) directly stimulated by LPS and which release mediators (chemokines) inducing extravasation. neutrophils and their attraction to activated mononuclear cells.

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  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pulmonology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention relates to the use of a pyrazole derivative for producing medicaments that are useful in preventing and treating chronic bronchitis and chronic obstructive bronchopneumopathy.

Description

UTILISATION D'UN DERIVE DU PYRAZOLE, POUR LA PREPARATION DE MEDICAMENTS UTILES DANS LA PREVENTION ET LE TRAITEMENT DE LA BRONCHITE CHRONIQUE ET DE LA BRONCHO-PNEUMOPATHIE CHRONIQUE OBSTRUCTIVE USE OF A PYRAZOLE DERIVATIVE FOR THE PREPARATION OF MEDICINES USEFUL IN THE PREVENTION AND TREATMENT OF CHRONIC BRONCHITIS AND CHRONIC OBSTRUCTIVE PNEUMOPATHY
La, présente invention a pour objet l'utilisation d'un composé antagoniste des récepteurs CBj aux cannabinoïdes, dérivé du pyrazole, pour la préparation de médicaments utiles dans la prévention et le traitement de la bronchite chronique et de la brortcho-pneumopathie chronique obstructive (BPCO, COPD : de l'anglais chronic obstructive pulmonary disease). Les cannabinoïdes endogènes, tels que l'anandamide, produisent une profonde inhibition de la toux et de la contraction du musclé bronchique. On a observé que le cannabis fumé montre une activité broncho-dilatatrice et il est connu d'utiliser des agonistes aux récepteurs cannabinoïdes pour traiter différentes pathologies dont l'asthme bronchique (Tashkin DP, Shapiro BJ, Lee YE, Harper EC :The object of the present invention is the use of a cannabinoid CBj receptor antagonist compound, derived from pyrazole, for the preparation of medicaments useful in the prevention and treatment of chronic bronchitis and chronic obstructive pulmonary disease ( COPD, COPD: from English chronic obstructive pulmonary disease). Endogenous cannabinoids, such as anandamide, produce profound inhibition of coughing and contraction of the bronchial muscle. It has been observed that smoked cannabis shows broncho-dilating activity and it is known to use cannabinoid receptor agonists to treat various pathologies including bronchial asthma (Tashkin DP, Shapiro BJ, Lee YE, Harper EC:
Effects of smoked marihuana in experimentally induced ast ma, Am. Rev. Respir. Dis. 1975, 112 :377-386 ; Tashkin DP : Bronchial effects of aerolized delta-9- tetrahy rocannabinol in healthy and asthmatic subjects, Am. Rev. Resp. Dis. 1977, 115:57-65 ; Vachon L., Fitzgerald MX, Solliday NH et al. : Single-dose effects of marihuana smoke; bronchial dynamics and respiratory-center sensitivity in normal subjects, N.Engl.J.Med. 1973,288:985-989). L'existence de récepteurs aux cannabinoïdes dans les voies respiratoires est décrit dans la demande de brevet US 2002/0035150. Il est indiqué dans cette demande que le blocage des récepteurs aux cannabinoïdes CB^ par le SR 141716A n'a pas de conséquences bronchomotrices per se mais augmente significativement la bronchoconstriction et la toux provoquées par l'administration de capsaicine. Le blocage des récepteurs aux cannabinoïdes CB^ par le SR 141716A inhibe l'effet anti-inflammatoire de deux agonistes cannabinoïdes le HU210 et le WLN 55212-2 produit sur la migration des neutrophiles dans un modèle de péritonite chez la souris (Smith SR, Denhardt G, Terminelli C : The anti-inflammatory activities of cannabinoid receptor ligands in mouse peritonitis models, EUT. J. Pharmacol. 2001, 432 :107-119). De façon surprenante, on a maintenant trouvé que les antagonistes aux récepteurs CB dérivés du pyrazole, sont actifs au niveau broncho-pulmonaire et peuvent être utilisés dans le traitement de la bronchite chronique. Selon la présente invention, par antagoniste des récepteurs aux cannabinoïdes dérivés du pyrazole, on entend le N-pipéridino-5-(4-chlorophényl)-l- 2,4- dichlorophényl)-4-methylpyrazole-3-carboxamide connu sous le nom de code SR141716 et dont la dénomination commune internationale est rimonabant décrit dans le brevet européen 656354, et le N-pipéridino-5-(4-bromophényι)-l-C2,4- dichlorophényl)-4-éthylpyrazole-3-carboxamide décrit dans le brevet européen 1150961. Des études cliniques réalisées avec le rimonabant ont montré qu'il réduit la faim, la prise calorique, et le poids corporel de patients obèses (G. Le Fur, 2003, 35, First European Workshop on Cannabinoid Research, Madrid, Spain, 4-5 avril 2003 etEffects of smoked marihuana in experimentally induced ast ma, Am. Rev. Respir. Dis. 1975, 112: 377-386; Tashkin DP: Bronchial effects of aerolized delta-9- tetrahy rocannabinol in healthy and asthmatic subjects, Am. Rev. Resp. Dis. 1977, 115: 57-65; Vachon L., Fitzgerald MX, Solliday NH et al. : Single-dose effects of marihuana smoke; bronchial dynamics and respiratory-center sensitivity in normal subjects, N.Engl.J.Med. 1973.288: 985-989). The existence of cannabinoid receptors in the respiratory tract is described in patent application US 2002/0035150. It is indicated in this application that the blocking of CB ^ cannabinoid receptors by SR 141716A has no bronchomotor consequences per se but significantly increases the bronchoconstriction and cough caused by the administration of capsaicin. Blockade of CB ^ cannabinoid receptors by SR 141716A inhibits the anti-inflammatory effect of two cannabinoid agonists HU210 and WLN 55212-2 produced on the migration of neutrophils in a peritonitis model in mice (Smith SR, Denhardt G, Terminelli C: The anti-inflammatory activities of cannabinoid receptor ligands in mouse peritonitis models, EUT. J. Pharmacol. 2001, 432: 107-119). Surprisingly, it has now been found that the CB receptor antagonists derived from pyrazole are active at the bronchopulmonary level and can be used in the treatment of chronic bronchitis. According to the present invention, the term “cannabinoid receptor antagonist derived from pyrazole” means N-piperidino-5- (4-chlorophenyl) -l- 2,4- dichlorophenyl) -4-methylpyrazole-3-carboxamide known by the name SR141716 and whose international common name is rimonabant described in European patent 656354, and N-piperidino-5- (4-bromophényι) -l-C2,4- dichlorophenyl) -4-ethylpyrazole-3-carboxamide described in European patent 1150961. Clinical studies carried out with rimonabant have shown that it reduces the hunger, the caloric intake and the body weight of obese patients (G. Le Fur, 2003, 35, First European Workshop on Cannabinoid Research, Madrid , Spain, 4-5 April 2003 and
Drugs RD, 2002, 3 (1), 65-66). Les résultats de l'étude clinique STRATUS dans le tabagisme ont montré qixe le rimonabant facilite l'arrêt de la consommation de tabac (Annual Scientific Session Am. Coll. Cardiol., 9 mars 2003, Nouvelle-Orléans). II a maintenant été trouvé que les antagonistes des récepteurs CBi aux cannabinoïdes dérivés du pyrazole choisis parmi le rimonabant et le N-pipéridino-5- (4-bromophényl)- 1 -(2,4-dichlorophényl)-4-éthylpyrazole-3 -carboxamide, sont actifs au niveau broncho-pulmonaire. Ainsi, selon la présente invention, un composé antagoniste des récepteurs CBj aux cannabinoïdes, dérivés du pyrazole, peut être utilisé pour la préparation de médicaments utiles pour prévenir et traiter les bronclαites chroniques et la broncho-pneumopathie chronique obstructive ainsi que la bronc hite chronique associée à la broncho-pneumopathie chronique pulmonaire. Les compositions pharmaceutiques selon la présente invention contiennent une dose efficace d'un composé antagoniste des récepteurs CB aux cannabinoïdes, dérrivé du pyrazole, ainsi qu'au moins un excipient pharmaceutiquement acceptable. Lesdits excipients sont choisis selon la forme pharmaceutique et le nxode d'administration souhaité, parmi les excipients habituels qui sont connus de l'Homme du métier. Dans les compositions pharmaceutiques de la présente invention pour l'administration orale, sublinguale, sous-cutanée, intramusculaire, intra-veinexise, topique, locale, intratrachéale, intranasale, transdermique ou rectale, le principe actif peut être administré sous forme unitaire d'administration, en mélange avec des excipients pharmaceutiques classiques, aux animaux et aux êtres humains pou r la prévention ou le traitement des troubles ou des maladies ci-dessus. Les formes unitaires d'administration appropriées comprennent les formes par voie orale telles que les comprimés, les gélules molles ou dures, les poudres, les granules et les solutions ou suspensions orales, les formes d'administration sublinguale, buccale, intratrachéale, intraoculaire, intranasale, par inhalation, les formes d'administration topique, transdermique, sous-cutanée, intramusculaire ou intraveineuse, les formes d'administration rectale et les implants. Pour l'application topique, on peut utiliser les composés selon l'invention dans des crèmes, gels, pommades ou lotions. EXEMPLE 1 : modèle animal Migration des cellules dans l'espace bronchoalvéolaire après activation par le E PS (lipopolysaccharide) bactérien. Des souris de 28 à 30 g sont stimulées par une exposition intratrachéale de 10> μg de LPS. 24 heures après l'injection de LPS, les animaux sont anesthésiés au pentobarbital et on réalise un lavage bronchoalvéolaire. On récupère les fluides de lavage, on les centrifuge puis on remet les cellules en suspension. On compte le nombre de cellules en différentiant, d'après les critères morphologiques standard, les cellules éosinophiles, neutrophiles et mononucléaires. L'injection intratrachéale de LPS induit une augmentation importante du nombre des cellules mononucléaires et neutrophiles dans l'espace bronchoalvéolaire des souris. On étudie l'effet du traitement par le rimonabant sur le recrutement, induit par le LPS, de ces cellules. Le rimonabant est administré aux animaux 1 heure avant le LPS à des doses variant de 0,3 à 30 mg/kg/i.p. La dose efficace 50 (DE50) qui inhibe la migration des cellules neutrophiles à plus de 80% est 2,3 (+ 0,3) mg/kg. L'inhibition de la migration cellulaire est comparable sur les cellules mononucléaires : DE50 égale à 1,9 (+ 0,5) mg/kg. Ce modèle induit par le LPS bactérien est classiquement utilisé, en particulier- au niveau broncho-pulmonaire, où il produit une infiltration des cellules neutrophiles polymorphonucléaires dans les tissus bronchopulmonaires suivie d'une libération, de médiateurs qui entraînent des lésions tissulaires. Cette infiltration des neutrophiles est la conséquence de l' activation des cellules mononucléaires (macrophages qui constituent la première barrière de défense au niveau de l'épithélium bronchique et lymphocytes T) stimulées directement par le LPS et qui libèrent des médiateurs (chemokines) induisant une extravasation des neutrophiles et une attraction de ces derniers vers les cellules mononucléaires activées. Cette séquence d'événements est tout à fait caractéristique de la pathogenèse de la broncho-pneumopathie chroni [ue obstructive induite par la fumée de cigarette et la pollution atmosphérique (Global Strategy for the diagnosis, management, and prévention of COPD, National Heart, Lung and Blood Institute, WHO, Executive Sunrmary of April 1998 Meeting). En conclusion, l'effet inhibiteur du rimonabant sur la migration à la fois des cellules mononucléaires et des cellules neutrophiles au niveau broncho-pulmonaire, après activation induite par le LPS bactérien, justifie d'un intérêt thérapeutique dans l'indication bronchite chronique et broncho-pneumopathie chronique obstructive. Drugs RD, 2002, 3 (1), 65-66). The results of the STRATUS clinical study in smoking have shown that rimonabant makes it easier to quit smoking (Annual Scientific Session Am. Coll. Cardiol., March 9, 2003, New Orleans). It has now been found that the cannabinoid CBi receptor antagonists derived from pyrazole chosen from rimonabant and N-piperidino-5- (4-bromophenyl) - 1 - (2,4-dichlorophenyl) -4-ethylpyrazole-3 - carboxamide, are active at the bronchopulmonary level. Thus, according to the present invention, a compound which is a CBj cannabinoid receptor antagonist, derived from pyrazole, can be used for the preparation of medicaments useful for preventing and treating chronic bronchialitis and chronic obstructive pulmonary disease as well as the associated chronic brown hite. to chronic pulmonary bronchopneumopathy. The pharmaceutical compositions according to the present invention contain an effective dose of a cannabinoid CB receptor antagonist compound, derived from pyrazole, as well as at least one pharmaceutically acceptable excipient. Said excipients are chosen according to the pharmaceutical form and the nxode of administration desired, from the usual excipients which are known to those skilled in the art. In the pharmaceutical compositions of the present invention for oral, sublingual, subcutaneous, intramuscular, intravenous, topical, local, intratracheal, intranasal, transdermal or rectal administration, the active principle can be administered in unit administration form , in admixture with conventional pharmaceutical excipients, to animals and humans for the prevention or treatment of the above disorders or diseases. Suitable unit dosage forms include oral forms such as tablets, soft or hard capsules, powders, granules and oral solutions or suspensions, sublingual, buccal, intratracheal, intraocular, intranasal, inhalation administration forms, topical, transdermal, subcutaneous, intramuscular or intravenous administration forms, rectal administration forms and implants. For topical application, the compounds according to the invention can be used in creams, gels, ointments or lotions. EXAMPLE 1: animal model Migration of cells into the bronchoalveolar space after activation by bacterial E PS (lipopolysaccharide). 28 to 30 g mice are stimulated by an intratracheal exposure of 10> μg of LPS. 24 hours after the LPS injection, the animals are anesthetized with pentobarbital and a bronchoalveolar lavage is carried out. The washing fluids are recovered, centrifuged and then the cells are resuspended. The number of cells is counted by differentiating, according to standard morphological criteria, the eosinophilic, neutrophilic and mononuclear cells. Intratracheal injection of LPS induces a significant increase in the number of mononuclear and neutrophil cells in the bronchoalveolar space of mice. We are studying the effect of rimonabant treatment on LPS-induced recruitment of these cells. Rimonabant is administered to animals 1 hour before LPS in doses varying from 0.3 to 30 mg / kg / ip The effective dose 50 (ED 50 ) which inhibits the migration of neutrophil cells by more than 80% is 2.3 (+ 0.3) mg / kg. The inhibition of cell migration is comparable on mononuclear cells: ED 50 equal to 1.9 (+ 0.5) mg / kg. This model induced by bacterial LPS is conventionally used, in particular in the bronchopulmonary level, where it produces an infiltration of polymorphonuclear neutrophil cells into the bronchopulmonary tissues followed by a release, of mediators which cause tissue damage. This neutrophil infiltration is the consequence of the activation of mononuclear cells (macrophages which constitute the first defense barrier at the level of the bronchial epithelium and T lymphocytes) directly stimulated by LPS and which release mediators (chemokines) inducing extravasation. neutrophils and their attraction to activated mononuclear cells. This sequence of events is entirely characteristic of the pathogenesis of chronic obstructive pulmonary disease induced by cigarette smoke and air pollution (Global Strategy for the diagnosis, management, and prevention of COPD, National Heart, Lung and Blood Institute, WHO, Executive Sunrmary of April 1998 Meeting). In conclusion, the inhibitory effect of rimonabant on the migration of both mononuclear cells and neutrophil cells at the bronchopulmonary level, after activation induced by bacterial LPS, justifies a therapeutic interest in the indication of chronic bronchitis and broncho -Chronic obstructive pulmonary disease.

Claims

REVENDICATIONS
1. Utilisation d'un composé antagoniste des récepteurs CBj aux cannabinoïdes, dérivé de pyrazole, choisi parmi le rimonabant et le N-pipéridino-5-(4- bromophényl)- 1 -(2,4-dichlorophényl)-4-ethylpyrazole-3 -carboxamide pour la préparation de médicaments utiles dans le traitement et la prévention de la bronchite chronique et de la broncho-pneumopathie chronique obstructive.1. Use of a cannabinoid CBj receptor antagonist compound, derived from pyrazole, chosen from rimonabant and N-piperidino-5- (4-bromophenyl) - 1 - (2,4-dichlorophenyl) -4-ethylpyrazole- 3 -carboxamide for the preparation of drugs useful in the treatment and prevention of chronic bronchitis and chronic obstructive pulmonary disease.
2. Utilisation selon la revendication 1 dans laquelle le composé antagoniste des récepteurs CB\ aux cannabinoïdes est le rimonabant.2. Use according to claim 1, in which the cannabinoid CB receptor antagonist compound is rimonabant.
3. Utilisation selon la revendication 1 dans laquelle le composé antagoniste des récepteurs CBj aux cannabinoïdes est le N-pipéridino-5-(4-bromophényl)-l-(-2,4- dichlorophényl)-4-ethylpyrazole-3-carboxamide. 3. Use according to claim 1 in which the cannabinoid CBj receptor antagonist compound is N-piperidino-5- (4-bromophenyl) -1 - (- 2,4-dichlorophenyl) -4-ethylpyrazole-3-carboxamide.
EP05739605A 2004-03-17 2005-03-15 Use of a pyrazole derivative for producing medicaments that are useful in preventing and treating chronic bronchitis and chronic obstructive bronchopneumopathy Withdrawn EP1729765A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0402824A FR2867685B1 (en) 2004-03-17 2004-03-17 USE OF A PYRAZOLE DERIVATIVE FOR THE PREPARATION OF DRUGS USEFUL IN THE PREVENTION AND TREATMENT OF CHRONIC BRONCHITIS AND OBSTRUCTIVE CHRONIC BRONCHO PNEUMOPATHY
PCT/FR2005/000620 WO2005099690A1 (en) 2004-03-17 2005-03-15 Use of a pyrazole derivative for producing medicaments that are useful in preventing and treating chronic bronchitis and chronic obstructive bronchopneumopathy

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AU (1) AU2005232415A1 (en)
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CA (1) CA2558331A1 (en)
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GB2431105A (en) * 2005-10-12 2007-04-18 Gw Pharma Ltd Cannabinoids for the treatment of pulmonary disorders
AU2007336068B2 (en) * 2006-12-18 2013-05-02 7Tm Pharma A/S Modulators of CB1 receptors

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FR2692575B1 (en) * 1992-06-23 1995-06-30 Sanofi Elf NOVEL PYRAZOLE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM.
FR2789079B3 (en) * 1999-02-01 2001-03-02 Sanofi Synthelabo PYRAZOLECARBOXYLIC ACID DERIVATIVE, ITS PREPARATION, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME
US6509367B1 (en) * 2001-09-22 2003-01-21 Virginia Commonwealth University Pyrazole cannabinoid agonist and antagonists

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US20080081827A1 (en) 2008-04-03
JP2007529481A (en) 2007-10-25
CA2558331A1 (en) 2005-10-27
FR2867685A1 (en) 2005-09-23
AU2005232415A1 (en) 2005-10-27
CN1933831A (en) 2007-03-21
WO2005099690A1 (en) 2005-10-27
AR049475A1 (en) 2006-08-09
IL178004A0 (en) 2006-12-31
TW200538441A (en) 2005-12-01
FR2867685B1 (en) 2008-05-23
KR20060124763A (en) 2006-12-05
BRPI0508714A (en) 2007-08-07

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