WO1997021439A1 - Medicament destine au traitement des troubles obsessifs compulsifs, de l'apnee du sommeil, des dysfonctions sexuelles, de l'emese et du mal des transports - Google Patents

Medicament destine au traitement des troubles obsessifs compulsifs, de l'apnee du sommeil, des dysfonctions sexuelles, de l'emese et du mal des transports Download PDF

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Publication number
WO1997021439A1
WO1997021439A1 PCT/EP1996/005736 EP9605736W WO9721439A1 WO 1997021439 A1 WO1997021439 A1 WO 1997021439A1 EP 9605736 W EP9605736 W EP 9605736W WO 9721439 A1 WO9721439 A1 WO 9721439A1
Authority
WO
WIPO (PCT)
Prior art keywords
butyl
piperazinyl
pyrimidinyl
pyrazole
imidazole
Prior art date
Application number
PCT/EP1996/005736
Other languages
English (en)
French (fr)
Inventor
Jordi Frigola-Constansa
Original Assignee
Laboratorios Del Dr. Esteve, S.A.
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 Laboratorios Del Dr. Esteve, S.A. filed Critical Laboratorios Del Dr. Esteve, S.A.
Priority to PL96321779A priority Critical patent/PL321779A1/xx
Priority to IL12146196A priority patent/IL121461A0/xx
Priority to EP96944029A priority patent/EP0808166A1/de
Priority to JP9521756A priority patent/JPH11501051A/ja
Priority to AU13764/97A priority patent/AU716665B2/en
Publication of WO1997021439A1 publication Critical patent/WO1997021439A1/fr
Priority to NO973589A priority patent/NO973589L/no
Priority to MXPA/A/1997/006133A priority patent/MXPA97006133A/xx

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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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to the use of 1- ⁇ 4- [4-aryl (or heteroaryl) -1-piperazinyl] -butyl ⁇ - 1-H-azole derivatives as well as their physiologically acceptable salts, for the manufacture of medicaments for the treatment of obsessive-compulsive disorder, sleep apnea, sexual dysfunction, Pemesis and motion sickness.
  • the aryl (or heteroaryl) - piperazinyl-butyl-azole derivatives show anti-obsessive activity, preventive of sleep apnea, which facilitates sexual, anti-magnetic and anti-nausea behavior and therefore they are useful in therapy for the prevention and treatment of obsessive-compulsive disorder, sleep apnea, sexual dysfunction and nausea and vomiting, in particular induced by chemotherapy and / or cytotoxic radiotherapy (s) or movement.
  • the compounds are intended for preventive or curative treatments in humans and in animals for depression, obsessive compulsive disorders, sleep apnea, sexual dysfunctions, emesis and motion sickness.
  • Ar represents an aromatic radical, nitrogenous or not, chosen from differently substituted aryls, 2-pyrimidine differently substituted, and 3- (1, 2-benzisothiazole),
  • Z1 represents a nitrogen atom or a substituted or unsubstituted carbon atom, which can be represented by: CR 1 ,
  • Z2 represents a nitrogen atom or a substituted or unsubstituted carbon atom, which can be represented by: CR 2 ,
  • Z4 represents a nitrogen atom or a substituted or unsubstituted carbon atom, which can be represented by: CR 4 ,
  • R 1 , R 2 , R 3 and R 4 identical or different, which can also form part of another cycle, aromatic or not, represent a hydrogen atom, a halogen, a lower alkyl radical, a nitro radical, a hydroxy radical, an alkoxy radical, a cyano radical, a hydroxycarbonyl radical, an alkoxycarbonyl radical, an aryl or substituted aryl radical, a sulfonic radical, a sulfonamido radical, an aminocarbonyl radical, substituted or not on the amino group, an amino radical or substituted amino,
  • Ar represents a differently substituted aryl, it is preferably a radical of formula
  • alkyl is understood to mean, according to the invention, lower alkyls, preferably C 1 -C 6 , linear or branched, optionally unsaturated, in particular methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl radicals and their different isomers. This definition also applies to the alkyl residues of the alkoxy.
  • halogen is meant according to the present invention preferably fluorine, chlorine, bromine or iodine.
  • aryl is understood in particular according to the invention an aromatic or heteroaromatic radical, in particular chosen from the radicals phenyl, naphthyl, anthryl, phenanthryl, pyridyl, pyrimidyl, etc., preferably phenyl, optionally substituted, in particular by one or more radicals selected from halogens, lower alkyl radicals, nitro, hydroxy, alkoxy, cyano, hydroxycarbonyl, alkoxycarbonyl , aryl or substituted aryl, sulfonic, sulfonamido, aminocarbonyl, substituted or not on the amino, amino or substituted amino group.
  • aromatic or heteroaromatic radical in particular chosen from the radicals phenyl, naphthyl, anthryl, phenanthryl, pyridyl, pyrimidyl, etc., preferably phenyl, optionally substituted, in particular by one or more radicals selected from halogens, lower
  • the substituents of the amino group are in particular alkyl or aryl radicals.
  • therapeutically acceptable salts is meant the usual salts of addition of organic or inorganic acids, such as hydrochlorides, dihydrochlorides, mesylates or tosylates.
  • serotonin (5-HT) is involved in the pathophysiology of affective disorders
  • pharmacological stimulation paradigms have been widely used to determine the "in vivo" dynamics of serotonin function in obsessive disorder compulsive, among others.
  • mice are placed in the illuminated compartment which becomes aversive to them and causes them a state of anxiety. This causes a flight response to the dark compartment, which may be associated with obsessive compulsive behavior.
  • the results obtained demonstrate that the lesopitron, at all the doses tested, delays the onset of obsessive-compulsive behavior of movement to the dark zone because the latency time clearly increases.
  • Sleep apnea includes a series of disorders of different magnitudes. Sleep apnea is classified as obstructive, central or mixed, depending on the presence or absence of respiratory effort during periods when the air flow is stopped. Obstructive and mixed apneas are the most frequent. They present with obstructive sleep apnea syndrome, in which recurrent and sporadic collapse of the upper respiratory tract is observed during sleep. If the collapse is complete, there is no air flow through the nose and mouth, and breathing stops. The usual result is a partial awakening of sleep and a return to normal breathing. In many cases the patient does not remember these episodes of apnea, but he feels tired and sleepy during the day, for no apparent reason. These episodes of recurrent apnea with hypoxemia and fragmented sleep can lead to serious neurological and cardiac consequences.
  • the rat electroencephalographic sleep study demonstrated that the 5 mg / kg lesopitron significantly increases the latency of sleep, at the same time as it decreases the total sleep time, that is, it increases waking time.
  • lesopitron can be a respiratory stimulant with persistent effects during sleep. It is therefore indicated for the treatment of sleep apnea.
  • the etiology of sexual dysfunction may include psychological factors, interpersonal and situational reasons, physical factors and, also, side effects of pharmacological agents. Since sexual dysfunction can be from a wide variety of these underlying causes, which can range from purely psychogenic to completely physical, it would be unrealistic to hope that only one treatment modality could become effective in any case. In usual clinical practice, sexual dysfunction is treated by determining the underlying causes and treating them when possible. In many cases the identification of the underlying causes of male and female sexual dysfunction is very complex, or even cannot be determined with certainty. The psychopharmacological treatment of sexual dysfunction is currently in its infancy. The use of drugs for the treatment of sexual dysfunction has had little success, which is evidenced by the absence of a widely accepted and recognized treatment for this use.
  • the results obtained with the lesopitron demonstrate the activity of the product by facilitating the sexual behavior of the rats.
  • the compounds of the invention have been studied as to their effects on emesis in ferrets according to a method described by Costall et al. (Neuropharmacology, 1986, 25, 9S9-961).
  • Ferrets of both sexes were individually conditioned at 21 ⁇ 1 ° C and fed normally. They were then administered the compound of Example 32 or a vehicle subcutaneously as a pretreatment 15 minutes before administration of cisplatin (10 mg / kg i.v. by way of a fixed jugular cannula). The animals were observed at the start of emesis, and after, for 240 minutes. Emesis was characterized by rhythmic abdominal contractions, either associated with the expulsion of solid or liquid matter (i.e. vomiting), or not associated with the passage of material through the mouth (nausea). The number of episodes and nausea or vomiting were recorded.
  • the compound of Example 32 is capable of antagonizing the emesis induced by cisplatin ( Figure 1).
  • FIG. 1 The compound of Example 32 is capable of antagonizing the emesis induced by cisplatin in the ferret.
  • the animals were observed for 240 minutes.
  • a significant difference compared to V is indicated sP ⁇ 0.05 (Mann-Whitney U test).
  • the administration dose is of course a function of the severity of the condition to be treated. It will generally be between about 5 and about 100 mg / day.
  • the derivatives of the invention will, for example, be administered in the form of tablets, capsules, or else intravenously. Two specific dosage forms will be indicated below, by way of examples.
  • the present invention extends to the application of these compounds as medicaments, to the pharmaceutical compositions containing them and to their use for the manufacture of medicaments intended for the treatment of obsessive-compulsive disorder, sleep apnea, sexual dysfunction, emesis and motion sickness.
  • the manufacture of antiobsessive agents preventive of sleep apnea, which facilitate sexual behavior, antiemetic and anti-nausea.

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  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Reproductive Health (AREA)
  • Hospice & Palliative Care (AREA)
  • Otolaryngology (AREA)
  • Urology & Nephrology (AREA)
  • Endocrinology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
PCT/EP1996/005736 1995-12-12 1996-12-11 Medicament destine au traitement des troubles obsessifs compulsifs, de l'apnee du sommeil, des dysfonctions sexuelles, de l'emese et du mal des transports WO1997021439A1 (fr)

Priority Applications (7)

Application Number Priority Date Filing Date Title
PL96321779A PL321779A1 (en) 1995-12-12 1996-12-11 Drug for use in therapy of obsessive-compulsive neurosis, sleep apnoea, secsual activity disorders, vomiting and kinetosis
IL12146196A IL121461A0 (en) 1995-12-12 1996-12-11 Use of 1-[4-[4-aryl (or heteroaryl)-1-piperazinyl]butyl]-1H-azole derivatives
EP96944029A EP0808166A1 (de) 1995-12-12 1996-12-11 Arzneimittel zur behandlung von obsessiv-impulsiven erkrankungen wie schlafsapnoe, sexualfunktionsstörungen, erbrechen und reisekrankheit
JP9521756A JPH11501051A (ja) 1995-12-12 1996-12-11 強迫性障害、睡眠時無呼吸、性的機能障害、嘔吐および乗物酔いの処置を意図する医薬
AU13764/97A AU716665B2 (en) 1995-12-12 1996-12-11 Medicament intended to the treatment of obsessive compulsive troubles, sleep apnoea, sexual dysfunctions, emesa and transport sickness
NO973589A NO973589L (no) 1995-12-12 1997-08-04 Medikament for behandling av tvangstanke-tvangshandlingsproblemer, sövnapne, seksuelle funksjonsforstyrrelser, emesi og reisesyke
MXPA/A/1997/006133A MXPA97006133A (es) 1995-12-12 1997-08-11 Uso de los derivados de 1-{4-[4-aril(o heteroaril)-1-piperazinil]-butil}-1h-azol para la preparacion de un medicamento destinado al tratamiento de lostrastornos obsesivo-compulsivos, de la apnea delsueño, de las disfunciones sexuales, de la emesis

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR95/14690 1995-12-12
FR9514690A FR2742052B1 (fr) 1995-12-12 1995-12-12 Utilisation des derives 1-(4-(4-aryl (ou heteroaryl)-1-piper azinyl)-buty)-1h-azole pour le traitement de la depression, des troubles obsessifs compulsifs, l'apnee du sommeil, les dysfonctions sexuelles, l'emese et le mal des transports

Publications (1)

Publication Number Publication Date
WO1997021439A1 true WO1997021439A1 (fr) 1997-06-19

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PCT/EP1996/005736 WO1997021439A1 (fr) 1995-12-12 1996-12-11 Medicament destine au traitement des troubles obsessifs compulsifs, de l'apnee du sommeil, des dysfonctions sexuelles, de l'emese et du mal des transports

Country Status (16)

Country Link
EP (1) EP0808166A1 (de)
JP (1) JPH11501051A (de)
CN (1) CN1177297A (de)
AR (1) AR004378A1 (de)
AU (1) AU716665B2 (de)
CA (1) CA2211161A1 (de)
CZ (1) CZ255197A3 (de)
ES (1) ES2134709B1 (de)
FR (1) FR2742052B1 (de)
HU (1) HUP9800198A2 (de)
IL (1) IL121461A0 (de)
NO (1) NO973589L (de)
PL (1) PL321779A1 (de)
TR (1) TR199700794T1 (de)
WO (1) WO1997021439A1 (de)
ZA (1) ZA9610457B (de)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2763950A1 (fr) * 1997-06-02 1998-12-04 Esteve Labor Dr 2- {4- [4-(4,5-dichloro-2-methylimidazol-1-yl)butyl] -1- piperazinyl }-5-fluoropyrimidine, sa preparation et son utilisation therapeutique
US6046331A (en) * 1998-12-17 2000-04-04 Synaptic Pharmaceutical Corporation Imidazolones and their use in treating benign prostatic hyperplasia and other disorders
US6579896B2 (en) 2000-09-06 2003-06-17 Ortho-Mcneil Pharmaceutical, Inc. Method for treating allergies using substituted pyrazoles
US6635633B2 (en) 2000-08-14 2003-10-21 Ortho-Pharmaceutical, Inc. Substituted pyrazoles
US6953793B2 (en) 2000-08-14 2005-10-11 Ortho-Mcneil Pharmaceutical, Inc. Substituted pyrazoles
WO2005094827A1 (en) * 2004-03-30 2005-10-13 Kestrel Pharmaceuticals Inc. Methods for treating sexual dysfunction
WO2006116614A1 (en) 2005-04-26 2006-11-02 Hypnion, Inc. Benzisoxazole piperidine compounds and methods of use thereof
WO2006116615A1 (en) 2005-04-26 2006-11-02 Hypnion, Inc. Benzisoxazole piperazine compounds and methods of use thereof
GB2435827A (en) * 2006-03-09 2007-09-12 Del Dr Esteve S A Spain Lab Use of substituted piperazine compounds for the treatment of food related disorders
US7309703B2 (en) 2000-08-14 2007-12-18 Ortho Mcneil Pharmaceutical, Inc. Substituted pyrazoles
US7332494B2 (en) 2000-08-14 2008-02-19 Janssen Pharmaceutica, N.V. Method for treating allergies using substituted pyrazoles

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW526202B (en) * 1998-11-27 2003-04-01 Shionogi & Amp Co Broad spectrum cephem having benzo[4,5-b]pyridium methyl group of antibiotic activity
WO2005030148A2 (en) 2003-09-25 2005-04-07 Cenomed, Inc. Tetrahydroindolone derivatives for treatment of neurological conditions
CN115304590B (zh) * 2022-09-19 2024-05-28 皮摩尔新药(辽宁)有限公司 2h-苯并三氮唑衍生物及其制备方法及含有它们的药物组合物

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0497659A1 (de) * 1991-01-28 1992-08-05 Laboratorios Del Dr. Esteve, S.A. Aryl(oder Heteroaryl)-piperazinyl-alkyl-azol-derivate, ihre Herstellung und ihre Anwendung als Medikament

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2723091B1 (fr) * 1994-07-29 1996-11-08 Esteve Labor Dr Tetrahydropyridine-(6,4-hydroxypiperidine) alkylazoles

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0497659A1 (de) * 1991-01-28 1992-08-05 Laboratorios Del Dr. Esteve, S.A. Aryl(oder Heteroaryl)-piperazinyl-alkyl-azol-derivate, ihre Herstellung und ihre Anwendung als Medikament

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
J.A. RUDD: "The effect of 5-HT1A receptor ligands on copper sulphate-induced emesis in the ferret.", BR. J. PHARMACOL., no. proc. suppl., 1993, pages 99p, XP000601371 *
M. BALLARIN: "Effect of acute administration of the 5-HT1A receptor ligand, lesopitron, on rat cortical 5-HT and dopamine turnover", BR. J. PHARMACOL., vol. 113, no. 2, 1994, pages 425 - 430, XP000578557 *
R.D. PORSOLT: "Serotonin: Neurotransmitter "à la mode".", PHARMACOPSYCHIATRY, vol. 26, no. 1, 1993, pages 20 - 24, XP000578409 *

Cited By (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2763950A1 (fr) * 1997-06-02 1998-12-04 Esteve Labor Dr 2- {4- [4-(4,5-dichloro-2-methylimidazol-1-yl)butyl] -1- piperazinyl }-5-fluoropyrimidine, sa preparation et son utilisation therapeutique
WO1998055476A1 (fr) * 1997-06-02 1998-12-10 Laboratorios Del Dr. Esteve, S.A. 2-{4-[4-(4,5-dichloro-2- methylimidazol-1-yl)butyl] -1-piperazinyl}-5-fluoropyrimidine, sa preparation et son utilisation therapeutique
ES2149691A1 (es) * 1997-06-02 2000-11-01 Esteve Labor Dr 2-4-[4-(4,5-dicloro-2metilimidazol-1-il)butil]-1-piperacinil -5-fluoropirimidina, su preparacion y su utilizacion terapeutica.
US6303608B1 (en) 1997-06-02 2001-10-16 Laboratorios Del Dr. Esteve, S.A. 2-{4-[4-(4,5-dichloro-2-methylimidazol-1-yl)butyl]-1-piperazinyl}-5-fluoropyrimidine, its preparation and its therapeutic use
US6346620B1 (en) 1997-06-02 2002-02-12 Laboratories Del Dr. Esteve S.A. Methods for preparation of 2-(4-(4-(4,5-dichloro-2-methylimidazol-1-yl)butyl)-1-piperazinyl)-5-fluoropyrimidine and salts thereof
US6046331A (en) * 1998-12-17 2000-04-04 Synaptic Pharmaceutical Corporation Imidazolones and their use in treating benign prostatic hyperplasia and other disorders
US6949540B2 (en) 2000-08-14 2005-09-27 Ortho-Mcneil Pharmaceutical, Inc. Substituted pyrazoles
US7589202B2 (en) 2000-08-14 2009-09-15 Ortho Mcneil Pharmaceutical, Inc. Substituted pyrazoles
US6635633B2 (en) 2000-08-14 2003-10-21 Ortho-Pharmaceutical, Inc. Substituted pyrazoles
US6936603B2 (en) 2000-08-14 2005-08-30 Ortho-Mcneil Pharmaceutical, Inc. Substituted pyrazoles
US7393850B2 (en) 2000-08-14 2008-07-01 Ortho Mcneil Pharmaceutical, Inc. Substituted pyrazoles
US6951851B2 (en) 2000-08-14 2005-10-04 Hui Cai Substituted pyrazoles
US6953793B2 (en) 2000-08-14 2005-10-11 Ortho-Mcneil Pharmaceutical, Inc. Substituted pyrazoles
US7772236B2 (en) 2000-08-14 2010-08-10 Ortho Mcneil Pharmaceutical, Inc. Substituted pyrazoles
US7452890B2 (en) 2000-08-14 2008-11-18 Ortho Mcneil Pharmaceutical, Inc. Substituted pyrazoles
US7429591B2 (en) 2000-08-14 2008-09-30 Ortho Mcneil Pharmaceutical, Inc. Substituted pyrazoles
US7265102B2 (en) 2000-08-14 2007-09-04 Ortho Mcneil Pharmaceutical, Inc. Substituted pyrazoles
US7417046B2 (en) 2000-08-14 2008-08-26 Ortho Mcneil Pharmaceutical, Inc. Substituted pyrazoles
US7309703B2 (en) 2000-08-14 2007-12-18 Ortho Mcneil Pharmaceutical, Inc. Substituted pyrazoles
US7332494B2 (en) 2000-08-14 2008-02-19 Janssen Pharmaceutica, N.V. Method for treating allergies using substituted pyrazoles
US7388011B2 (en) 2000-08-14 2008-06-17 Ortho Mcneil Pharmaceutical, Inc. Substituted pyrazoles
US6583155B2 (en) 2000-09-06 2003-06-24 Ortho-Mcneil Pharmaceutical, Inc. Method for treating allergies using substituted pyrazoles
US6579896B2 (en) 2000-09-06 2003-06-17 Ortho-Mcneil Pharmaceutical, Inc. Method for treating allergies using substituted pyrazoles
WO2005094827A1 (en) * 2004-03-30 2005-10-13 Kestrel Pharmaceuticals Inc. Methods for treating sexual dysfunction
WO2006116615A1 (en) 2005-04-26 2006-11-02 Hypnion, Inc. Benzisoxazole piperazine compounds and methods of use thereof
WO2006116614A1 (en) 2005-04-26 2006-11-02 Hypnion, Inc. Benzisoxazole piperidine compounds and methods of use thereof
US7494998B2 (en) 2005-04-26 2009-02-24 Hypnion, Inc. Benzisoxazole piperazine compounds and methods of use thereof
GB2435827A (en) * 2006-03-09 2007-09-12 Del Dr Esteve S A Spain Lab Use of substituted piperazine compounds for the treatment of food related disorders

Also Published As

Publication number Publication date
ES2134709B1 (es) 2000-05-16
EP0808166A1 (de) 1997-11-26
ES2134709A1 (es) 1999-10-01
JPH11501051A (ja) 1999-01-26
FR2742052A1 (fr) 1997-06-13
AR004378A1 (es) 1998-11-04
NO973589L (no) 1997-10-08
CN1177297A (zh) 1998-03-25
HUP9800198A2 (hu) 1999-09-28
IL121461A0 (en) 1998-02-08
CZ255197A3 (cs) 1998-01-14
CA2211161A1 (fr) 1997-06-19
NO973589D0 (no) 1997-08-04
AU716665B2 (en) 2000-03-02
TR199700794T1 (xx) 1997-11-21
FR2742052B1 (fr) 1998-04-10
ZA9610457B (en) 1997-06-24
PL321779A1 (en) 1997-12-22
AU1376497A (en) 1997-07-03
MX9706133A (es) 1997-11-29

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