EP1030666A1 - Nouvelle utilisation de composes a des fins antiprurigineuses - Google Patents

Nouvelle utilisation de composes a des fins antiprurigineuses

Info

Publication number
EP1030666A1
EP1030666A1 EP98953608A EP98953608A EP1030666A1 EP 1030666 A1 EP1030666 A1 EP 1030666A1 EP 98953608 A EP98953608 A EP 98953608A EP 98953608 A EP98953608 A EP 98953608A EP 1030666 A1 EP1030666 A1 EP 1030666A1
Authority
EP
European Patent Office
Prior art keywords
compound
xxaanntthhiinnee
bbuuttyyll
group
aammiinnoo
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.)
Withdrawn
Application number
EP98953608A
Other languages
German (de)
English (en)
Other versions
EP1030666A4 (fr
Inventor
Don E. Griswold
Siegfried Benjamin Christensen, Iv
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.)
SmithKline Beecham Ltd
Original Assignee
SmithKline Beecham Ltd
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 SmithKline Beecham Ltd filed Critical SmithKline Beecham Ltd
Publication of EP1030666A1 publication Critical patent/EP1030666A1/fr
Publication of EP1030666A4 publication Critical patent/EP1030666A4/fr
Withdrawn legal-status Critical Current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
    • A61K31/495—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
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • 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
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics

Definitions

  • the present invention relates to compounds which are of use in the treatment and management of pruritis.
  • Pruritis is a common symptom of many inflammatory skin diseases, notably psoriasis and atopic dermatitis. This symptom has historically been difficult to model. Recently, a behavioral model for peripherally evoked itch was published (Woodward et al., Characterization of a behavioral model for peripherally evoked itch suggests platelet-activating factor as a potent pruritogen. J. Pharmacol. Exp. Therap. 272:758- 765, 1995). This model has lead to additional modifications as will be shown herein. As little effective treatment for this condition exists, there remains a need for treatment, in this field, for compounds which are capable of anti-pruritic activity.
  • This invention relates to the novel use of PDE4 inhibitors, preferably compounds of Formula (I) for the prophylaxis, treatment and management of pruritis in a mammal, including humans, in need of such treatment, which method comprises administering to such mammal, an effective amount of a compound of Formula (I).
  • PDE4 inhibitors preferably compounds of Formula (I) for the prophylaxis, treatment and management of pruritis in a mammal, including humans, in need of such treatment, which method comprises administering to such mammal, an effective amount of a compound of Formula (I).
  • the compounds of the present invention of Formula (I) are described herein.
  • Figure I demonstrates the anti-pruritic activity of compound I. 1 ,3-di- cyclopropylmethyl-8-amino xanthine in an arachidonic acid induced pruritis model.
  • PDE4 inhibitors as a class of compounds, regardless of structure possess anti-pruritis activity As pruritis is a key symptom of many different disease states, the use of PDE4 inhibitors in the managment of pruritic activity is of great value. While it is recognized that PDE4 compounds are of many different structural classes, they all share a common feature, inhibition of the PDE4 isoenzymes.
  • PDE4 compounds for use herein include, but are not limited to, those desc ⁇ bed in WO 92/00968, PCT/US91/08229, WO 92/05175, WO 92/05176, WO 92/11260, WO 93/01014, PCT/US92/03613, WO 93/07111, PCT/US93/02045, WO 93/19748, WO 93/19750, WO 93/19751, WO 93/19747, WO 93/19749, WO 93/19720, WO 94/20079, WO 95/00139, WO 95/08581, WO 95/09308, WO 95/09623, WO 95/09836, WO 95/09624, WO 95/09837, WO 95/0
  • CP 80633 is describ-sd in J.M. Hanifin et al. J. Invest. Dermatol. 107:51-56 (1996).
  • the method of use does net include the compound CP80633.
  • the compounds of Formula (I) may also be used in association with the vete ⁇ nary treatment of mammals, other than in humans, in need of such treatment for pruritis Treatment, may be therapeutically or prophylactically in animals
  • Patent 5,734,05 1 are represented by the structure
  • Rl and R 2 are each independently alkyl or a moiety of the formula -(CH 2 ) m -A, m is a number from 0 to 3, A is an unsubstituted or substituted cyclic hydrocarbon radical R3 is halogen, nitro, or -NR 4 R 5 ;
  • R4 and R 5 are independently hydrogen, alkyl, alkylcarbonyl or together with the nitrogen to which they are attached forming an optionally substituted heterocyclic ring; and the pharmaceutically acceptable salts thereof.
  • both Ri and R2 represent -(CH2) m -A.
  • the A moiety represents a C 3 -8 cycloalkyl group, particularly a C3- 6 cycloalkyl and preferably unsubstituted. More preferably A is a cyclopropyl or cyclobutyl moiety.
  • m is zero or one.
  • Suitable optional substituent groups for any cyclic hydrocarbon include a Ci ⁇ alkyl moiety or halogen atom.
  • a preferred group for Ri or R 2 is an alkyl group of 1 to 6 carbons, specifically methyl, ethyl, propyl or n-butyl. More preferred is n-butyl.
  • R 3 is halogen
  • the preferred substitution is bromine or chlorine
  • R3 is -NR 4 R 5
  • R 4 and R5 represent alkyl or alkylcarbonyl
  • one of R4 or R 5 is hydrogen
  • Suitable heterocyclic groups include saturated or unsaturated heterocylic groups having single or fused rings, each ring having 5 to 7 ring atoms which ring atoms optionally comprise up to two additional hetero atoms selected from 0, N, or S.
  • Preferred heterocyclic groups include single rings comprising 5 to 7 ring atoms, more preferably 5 to 6 ring atoms,and most preferably 6 ring atoms
  • Preferred heterocyclic groups are pyrrolidinyl, piperidinyl, or morpholinyl rings
  • 1,3-d n-butyl-8-nitro xanthine 1,3-d •cyclopropylmethyl-8-nitro xanthine, 1,3-d cyclobutylmethyl-8-nitro xanthine; 1,3-d cyclopentylmethyl-8-nitro xanthine; 1,3-d cyclohexylmethyl-8-nitro xanthine, 1,3-d n-butyl-8-amino xanthine; 1,3-d -cyclopropylmethyl-8-amino xanthine, 1,3-d -cyclobutylmethyl-8-amino xanthine, 1,3-d -cyclopentylmethyl-8-amino xanthine; 1,3-d -cyclohexylmethyl-8-amino xanthine, 1,3-d: -cyclopropyl-8-amino xanthine; 1,3-d -n-butyl-8-acetamido
  • the most preferred compound of Formula (I) for use in the method of this invention is l,3-di-cyclopropylmethyl-8-amino xanthine or a pharmaceutically acceptable salt thereof.
  • alkyl groups as used herein alone or when used as part of another group (for example as in alkylcarbonyl) is meant to include both straight or branched chain radicals of 1 to 12 carbon atoms, unless the chain length is limited thereto, including, but not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, sec- butyl, isobutyl, tert-butyl, and the like.
  • cyclic hydrocarbon unless specified otherwise, as used herein is meant a single ring or a fused rings of 3 to 8 carbon atoms. Cyclic hydrocarbons may comprise up to 8 carbons in each ring.
  • cycloalkyl or “cycloalkyl alkyl” as used herein is meant to be interchangeable with the term “cyclic hydrocarbon”
  • Cycloalkyl and cycloalkyl-alkyl groups are meant to include, but not limited to cyclopropyl, cyclopropyl-methyl, cyclopentyl or cyclohexyl.
  • halo as used herein is meant all halogens, i.e.. chloro, fluoro, bromo and iodo.
  • the compounds of Formula (I) or a pharmaceutically acceptable salt thereof can also be used in the manufacture of a medicament for the prophylactic or therapeutic treatment of any disease state in a human, or other mammal, which is exacerbated or caused by excessive or or unregulated pruritic activity.
  • the compounds of Formula (I) may be used topically in the treatment or prophylaxis of topical disease states which have a pruritic component.
  • the compounds of Formula (I) are disclosed in Maschler et al.. Great Britain Patent Application No. 8906792.0 filed on March 23, 1989, and US Patent 5,734,051 for the treatment of disorders associated with increased numbers of eosinophils, such as proliferative skin disease states, i.e. psoriasis, atopic dermatitis, non-specific dermititis, primary irritant contact dermatitis, allergic contact dermititis, or allergic disorders such as atopy, uticaria, eczema, rhinitis, serborrheic dermatitis, and mange in domestic animals.
  • proliferative skin disease states i.e. psoriasis, atopic dermatitis, non-specific dermititis, primary irritant contact dermatitis, allergic contact dermititis, or allergic disorders such as atopy, uticaria, eczema, rhinitis, serborrheic dermatiti
  • the compounds of Formula (I) are also disclosed in PCT/US91/08734, and PCT US93/01496 published as WO 93/06699 whose dislosures are incorporated herein by reference in its entirety, for the treatment of tumour necrosis mediated diseases.
  • the compounds of Formula (I) may, be administered concurrently with another agents useful for the treatment or managment of pruritis, such as steroids.
  • a monokine activity interfering agent required for therapeutic effect will, of course, vary with the agent chosen, the route of administration desired, the nature and severity of the disease, and the particular condition of the mammal, specifically human, undergoing treatment, and is ultimately at the discretion of the physician. It will also be recognized by one of skill in the art that the optimal quantity and spacing of individual dosages of the agent will be determined by the nature and extent of the condition being treated, the form, route and site of administration, and the particular patient being treated, and that such optimums can be determined by conventional techniques.
  • the optimal course of treatment i.e., the number of doses of the agent given per day for a defined number of days
  • the compounds of Formula (I) may be administered orally (when active by this route), topically, parenterally or by inhalation in conventional dosage forms prepared by combining such agent with standard pharmaceutical earners according to conventional procedures in an amount sufficient to produce therapeutic activity
  • the pharmaceutical earner employed can be readily determined by one of skill in the art who will recognize that such determination will depend upon vanous well- known factors such as the nature, quantity and character of the particular monokine activity mterfenng agent being employed and the form and route of administration desired
  • the earners employed may be those desenbed elsewhere herein
  • the pharmaceutical composition of the present invention will comprise an effective, non-toxic amount of a compound of Formula (I) and a pharmaceutically acceptable earner or diluent
  • the compounds of Formula (I) are administered in conventional dosage forms prepared by combining a compound of Formula (I) in an amount sufficient to produce activity, respectively, with standard pharmaceutical earners according to conventional procedures These procedures may involve mixing, granulating and compressing or dissolving the ingredients as appropnate to the desired preparation
  • the pharmaceutical earner employed may be, for example either a solid or liquid Exemplary of solid earners are lactose, terra alba, sucrose talc, gelatin, agar pectin, acacia, magnesium stearate, steanc acid and the like Exemplary of liquid earners are syrup, peanut oil, olive oil, polyethylene glycol, coconut oil, water and the like
  • the earner or diluent may include time delay mate ⁇ al well known to the art such as glyceryl monostearate or glyceryl di
  • compositions of Formula (I) and their pharmaceutically acceptable salts can be employed in a wide vanety of pharmaceutical forms
  • the preparation of a pharmaceutically acceptable salt will be determined by the nature of the compound itself, and can be prepared by conventional techniques readily available to one skilled in the art
  • a solid earner if a solid earner is used, the preparation can be tableted, placed in a hard gelatin capsule in powder or pellet form or in the form of a troche or lozenge
  • the amount of solid earner will vary widely but preferably will be from about 25 mg to about 1 gram
  • the preparation will be in the form of a syrup, emulsion, soft gelatin capsule, stenle injectable liquid such as an ampule or nonaqueous liquid suspension
  • any routine encapsulation is suitable, for example using the aforementioned carriers in a hard gelatin capsule shell.
  • composition is in the form of a soft gelatin shell capsule
  • any pharmaceutical carrier routinely used for preparing dispersions or suspensions may be considered, for example aqueous gums, celluloses, silicates or oils and are incorporated in a soft gelatin capsule shell
  • a syrup formulation will generally consist of a suspension or solution of the compound or salt in a liquid carrier for example, ethanol, polyethylene glycol, coconut oil, glycerine or water with a flavouring or colouring agent.
  • the amount of a compound of Formula (I) required for therapeutic effect on topical administration will, of course, vary with the compound chosen, the nature and severity of the inflammatory condition and the animal undergoing treatment, and is ultimately at the discretion of the physician.
  • parenteral' as used herein includes intravenous, intramuscular, subcutaneous intranasal, intrarectal, intravaginal or intraperitoneal administration
  • the subcutaneous and intramuscular forms of parenteral administration are generally preferred. Appropriate dosage forms for such administration may be prepared by conventional techniques.
  • Typical parenteral compositions consist of a solution or suspension of the compound or salt in a sterile aqueous or non-aqueous carrier optionally containing a parenterally acceptable oil, for example polyethylene glycol, polyviny'pyrrolido ⁇ c, lecithin, arachis oil, or sesame oil
  • a parenterally acceptable oil for example polyethylene glycol, polyviny'pyrrolido ⁇ c, lecithin, arachis oil, or sesame oil
  • the daily dosage regimen for parenteral administration is suitably about 0 001 mg/Kg to 40 mg/Kg, preferably about 0 01 mg/Kg to 20 mg/Kg, of a compound of the formula (I) or a pharmaceutically acceptable salt thereof calculated as the free base
  • the compounds of Formula (I) may be administered orally
  • the daily dosage regimen for oral administration is suitably about 1 mg/kg to 1 OOOmg day
  • the dosage is suitably about 001 mg/kg to 40mg/kg, preferably about 0 01 to 20 mg/Kg of a compound of formula (I) or a pharmaceutically acceptable salt thereof calculated as the free base
  • the active ingredient may be administered from 1 to 6 times a day, sufficient to exhibit activity
  • the compounds of Formula (I) may also be administered by inhalation
  • inhalation is meant intranasal and oral inhalation administration
  • Appropriate dosage forms for such administration such as an aerosol formulation or a metered dose inhaler, may be prepared by conventional techniques.
  • the daily dosage regimen for inhalation administration is suitably about 001 mg/kg to 40mg/kg, preferably 0 01 to 20 mg/Kg of a compound of formula (I) or a pharmaceutically acceptable salt thereof calculated as the free base
  • Typical compositions for inhalation are in the form of a solution, suspension or emulsion that may be administered as a dry powder or in the form of an aerosol using a conventional propellant such as dichlorodifluoromethane or t ⁇ chlorofluoromethane
  • the composition is in unit dosage form, for example a tablet, capsule or metered aerosol dose, so that the patient may administer to himself a single dose
  • the compounds of Formula (I) may also be administered topically
  • Bv topical administration is meant non-systemic administration and includes the application of a
  • systemic administration oral, intravenous, intrapentoneal and intramuscular administration
  • the active ingredient may compnse, for topical administration, from 0 001% to 10% w/w e g from 1% to 2% by weight of the formulation although it may compnse as m u ch as 10% w/w but preferably not in excess of 5% w/w and more preferably from 0 1% to 1% w/w of the formulation
  • the topical formulations of the present invention comprise an active ingredient together with one or more acceptable carner(s) therefor and optionally any other therapeutic ⁇ ngred ⁇ ent(s)
  • the car ⁇ er(s) must be 'acceptable' in the sense of being compatible with the other ingredients of the formulation and not deletenous to the recipient thereof
  • Formulations suitable for topical administration include liquid or semi-liquid preparations suitable for penetration through the skin to the site of inflammation such as liniments, lotions, creams, ointments or pastes, and drops suitable for administration to the eye, ear or nose
  • Drops according to the present invention may comprise ste ⁇ le aqueous or oily solutions or suspensions and may be prepared by dissolving the active ingredient in a suitable aqueous solution of a bactencidal and/or fungicidal agent and/or any other suitable preservative, and preferably including a surface active agent
  • the resulting solution may then be clarified by filtration, transferred to a suitable container which is then sealed and ste ⁇ lized by autoclaving or maintaining at 98-100°C for half an hour
  • the solution may be sten zed by filtration and transfened to the container by an aseptic technique
  • bactencidal and fungicidal agents suitable for inclusion in the drops are phenylmercu ⁇ c nitrate or acetate (0 002%), benzalkonium chlonde (0 01%) and chlorhexidme acetate (0 01%)
  • Suitable solvents for the preparation of an oily solution include glycerol, diluted alcohol and propylene glycol
  • Lotions according to the present invention include those suitable for application to the skin or eye
  • An eye lotion may compnse a stenle aqueous solution optionally containing a bactencide and may be prepared by methods similar to those for the preparation of drops
  • Lotions or liniments for application to the skin may also include an agent to hasten drying and to cool the skin, such as an alcohol or acetone, and/or a moistu ⁇ zer such as glycerol or an oil such as castor oil or arachis oil
  • Creams, ointments or pastes according to the present invention are semi-solid formulations of the active ingredient for external application
  • Thev may be made by mixing the active ingredient in finely-divided or powdered form, alone or in solution or suspension in an aqueous or non-aqueous fluid, with the aid of suitable machinery with a greasy or non-greasy basis
  • the basis may compnse hydrocarbons such as hard, soft or liquid paraffin, glycerol, beeswax, a metallic soap, a mucilage, an oil of natural o ⁇ gm such as almond, corn, arachis, castor or olive oil, wool fat or its denvatives, or a fatty acid such as stenc or oleic acid together with an alcohol such as propylene glycol or macrogols
  • the formulation may incorporate any suitable surface active agent such as an anionic, catiomc or non-ionic surfactants such as sorbitan esters or polyoxyethylene denvatives thereof Suspending agents
  • the form and character of the pharmaceutically acceptable earner or diluent is dictated by the amount of active ingredient, a compound of Formula (I), with which it is to be combined, the route of administration and other well-known vanables
  • the optimal quantity and spacing of individual dosages of a compound of Formula (I) or a pharmaceutically acceptable salt thereof will be determined by the nature and extent of the condition being treated, the form, route and site of administration and the particular patient being treated, and that such optimums can be determined by conventional techniques
  • the optimal course of treatment 1 e the number of doses of a compound of Formula (I) or a pharmaceutically acceptable salt thereof given per day for a defined number of days, can be ascertained by those skilled in the art using conventional course of treatment determination tests.
  • Formulations for pharmaceutical use incorporating compounds of the present invention can be prepared in various forms and with numerous excipients. Examples of liquid formulations are given below.
  • a solution containing a compound of Formula (I) is prepared by dissolving the compound in water, or other suitable carrier, with or without a preservative, such as benzoic acid, to deliver the desired amount of drug per use
  • the compound is present in an amount from about lO ⁇ g to about 30 ⁇ g/ per ml of carrier
  • a solution containing a compound of Formula (I) is prepared by dissolving the compound in an amount from about 1 to about lOmg per ml of PEG 400 with or without BHA/BHT preservatives
  • the solution can alternatively be filled into a soft gelatin capsule to prepare a solid oral dosage form or used as a syrup
  • a solid dosage form containing a compound of Formula (I), such as 1,3-di- cyclopropylmethyl-8-amino xanthine has been prepared by mixing 50mg of the compound with various concentration (mg) of mannitol, hydroxypropylmethylcellulose, calipharm, Starch 1500, and magnesium sterate (as a lubricant), to fill capsules of an appropriate size or the composition may, if desired, be compressed into tablets
  • a compound of Formula (I) such as 1,3-di- cyclopropylmethyl-8-amino xanthine
  • the mouse model takes advantage of the cutaneous inflammatory response to arachidonic acid which is preceeded by scratching and rubbing behavior indicative of pruritis.
  • mice were administered a topical dose of arachidonic acid (2 mg/ear) in 20 ul cold acetone to the left ear.
  • the treated mice were then placed individually into 4L beakers. After a 2 min accommodation period, the episodes of scratching and head shaking were counted over a 10 min period.
  • the data were analysed by calculating the mean and standard error. A statistical difference in the mean values was determined using Student's t-test.
  • the biochemical pharmacology of the inflammatory response to arachidonic acid has implicated mast cell degranulation and eicosanoid inflammatory mediator release (e.g. leukotrienes and prostanoids). Tachykinins and platelet activating factor may also be involved in this response.
  • PDE4 phosphodiesterase type 4
  • BRL 61063 is the same as Compound I.

Landscapes

  • Health & Medical Sciences (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)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Cette invention se rapporte à des dérivés de xanthines 8-substituées, qui sont utilisés dans la prophylaxie ou le traitement de maladies ou de troubles qui ont une composante prurigineuse.
EP98953608A 1997-10-17 1998-10-16 Nouvelle utilisation de composes a des fins antiprurigineuses Withdrawn EP1030666A4 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US6374697P 1997-10-17 1997-10-17
US63746P 1997-10-17
PCT/US1998/021886 WO1999020280A1 (fr) 1997-10-17 1998-10-16 Nouvelle utilisation de composes a des fins antiprurigineuses

Publications (2)

Publication Number Publication Date
EP1030666A1 true EP1030666A1 (fr) 2000-08-30
EP1030666A4 EP1030666A4 (fr) 2002-10-16

Family

ID=22051225

Family Applications (1)

Application Number Title Priority Date Filing Date
EP98953608A Withdrawn EP1030666A4 (fr) 1997-10-17 1998-10-16 Nouvelle utilisation de composes a des fins antiprurigineuses

Country Status (18)

Country Link
EP (1) EP1030666A4 (fr)
JP (1) JP2001520196A (fr)
KR (1) KR20010031149A (fr)
CN (1) CN1306426A (fr)
AR (1) AR015966A1 (fr)
AU (1) AU740875B2 (fr)
BR (1) BR9814080A (fr)
CA (1) CA2306985A1 (fr)
CO (1) CO4810374A1 (fr)
CZ (1) CZ20001376A3 (fr)
HU (1) HUP0003792A3 (fr)
IL (1) IL135581A0 (fr)
NO (1) NO20001847L (fr)
NZ (1) NZ503551A (fr)
PL (1) PL341062A1 (fr)
TR (1) TR200001040T2 (fr)
WO (1) WO1999020280A1 (fr)
ZA (1) ZA989450B (fr)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE60113731T2 (de) 2001-01-31 2006-06-29 Pfizer Products Inc., Groton Als inhibitoren von pde4-isozymen geeignete etherderivate
US7250518B2 (en) 2001-01-31 2007-07-31 Pfizer Inc. Nicotinamide acids, amides, and their mimetics active as inhibitors of PDE4 isozymes
KR20030072614A (ko) 2001-01-31 2003-09-15 화이자 프로덕츠 인크. Ｐｄｅ４ 이소자임 억제제로 유용한 티아졸릴-,옥사졸릴-, 피롤릴- 및 이미다졸릴-산 아미드 유도체
CA2436535A1 (fr) 2001-01-31 2002-08-08 Prizer Products Inc. Derives de biaryl nicotinamide utiles comme inhibiteurs d'isozymes de pde4
US20030175314A1 (en) * 2001-11-19 2003-09-18 Didriksen Erik Johannes Pharmaceutical composition for dermal application
US20060258703A1 (en) * 2003-07-17 2006-11-16 Ono Pharmaceutical Co., Ltd. Remedy for pruritus comprising piperidine derivative as the active ingredient
WO2005053672A1 (fr) * 2003-12-04 2005-06-16 Santen Pharmaceutical Co., Ltd. Remede contre le prurit comportant du cilomilaste ou un sel de celui-ci comme principe actif
JP2005187458A (ja) * 2003-12-04 2005-07-14 Santen Pharmaceut Co Ltd シロミラストまたはその塩を有効成分とする掻痒治療剤
JP5001012B2 (ja) 2004-02-14 2012-08-15 グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー Ｈｍ７４ａ受容体活性を有する薬剤
JP2008137892A (ja) * 2005-03-04 2008-06-19 Eisai Co Ltd 止痒剤
EP2272848B1 (fr) 2005-08-10 2012-12-26 Glaxosmithkline LLC Dérivés de la xanthine en tant qu'agonistes sélectifs du HM74A
TWI404709B (zh) * 2006-02-21 2013-08-11 Eisai R&D Man Co Ltd 4- (3-benzamidophenyl) -6,7-dimethoxy-2-methylamine quinazoline derivatives
AU2007218725B2 (en) * 2006-02-21 2011-12-01 Eisai R & D Management Co., Ltd. 4-(3-benzoylaminophenyl)-6,7-dimethoxy-2- methylaminoquinazoline derivative
CA2678477A1 (fr) 2007-02-16 2008-08-21 Eisai R&D Management Co., Ltd. Cristal, forme amorphe et sel d'acide terephtalique de methyle n-[3-(6,7-dimethoxy- 2-methylaminoquinazoline-4-yl)phenyle]
EP2202229B1 (fr) 2007-08-17 2012-03-14 Eisai R&D Management Co., Ltd. Nouvelle préparation pour une utilisation externe
ATE538102T1 (de) 2007-08-17 2012-01-15 Eisai R&D Man Co Ltd Verfahren zur herstellung eines chinazolinderivats
ES2659458T3 (es) 2011-06-28 2018-03-15 Mitsubishi Tanabe Pharma Corporation Compuestos de naftaleno para tratar el prurito
WO2016119570A1 (fr) 2015-01-30 2016-08-04 上海珊顿医药科技有限公司 Prévention ou traitement de maladie de goutte ou d'acide urique

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997035854A1 (fr) * 1996-03-26 1997-10-02 Byk Gulden Lomberg Chemische Fabrik Gmbh Nouvelles phenanthridines substituees en position 6
WO1997043288A1 (fr) * 1996-05-15 1997-11-20 Byk Gulden Lomberg Chemische Fabrik Gmbh Nouvelles imidazopyridines
WO1998040382A1 (fr) * 1997-03-07 1998-09-17 Byk Gulden Lomberg Chemische Fabrik Gmbh Nouveaux composes tetrazoles
WO1998041232A2 (fr) * 1997-03-18 1998-09-24 Basf Aktiengesellschaft Procedes et compositions permettant de moduler la sensibilite aux corticosteroides
WO1998055481A1 (fr) * 1997-06-03 1998-12-10 Byk Gulden Lomberg Chemische Fabrik Gmbh Benzonaphthyridine

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2098846A1 (fr) * 1990-12-21 1992-06-22 David G. Smith Derives de la xanthine

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997035854A1 (fr) * 1996-03-26 1997-10-02 Byk Gulden Lomberg Chemische Fabrik Gmbh Nouvelles phenanthridines substituees en position 6
WO1997043288A1 (fr) * 1996-05-15 1997-11-20 Byk Gulden Lomberg Chemische Fabrik Gmbh Nouvelles imidazopyridines
WO1998040382A1 (fr) * 1997-03-07 1998-09-17 Byk Gulden Lomberg Chemische Fabrik Gmbh Nouveaux composes tetrazoles
WO1998041232A2 (fr) * 1997-03-18 1998-09-24 Basf Aktiengesellschaft Procedes et compositions permettant de moduler la sensibilite aux corticosteroides
WO1998055481A1 (fr) * 1997-06-03 1998-12-10 Byk Gulden Lomberg Chemische Fabrik Gmbh Benzonaphthyridine

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DATABASE CA [Online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; COHAN, V. L. ET AL: "In vitro pharmacology of the novel phosphodiesterase type 4 inhibitor, CP - 80633" retrieved from STN Database accession no. 125:237990 CA XP002210532 & JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS (1996), 278(3), 1356-1361 , 1996, *
See also references of WO9920280A1 *

Also Published As

Publication number Publication date
HUP0003792A2 (hu) 2001-10-28
NO20001847D0 (no) 2000-04-10
IL135581A0 (en) 2001-05-20
JP2001520196A (ja) 2001-10-30
NO20001847L (no) 2000-04-10
NZ503551A (en) 2002-05-31
ZA989450B (en) 1999-04-19
PL341062A1 (en) 2001-03-26
KR20010031149A (ko) 2001-04-16
AU1093899A (en) 1999-05-10
EP1030666A4 (fr) 2002-10-16
CO4810374A1 (es) 1999-06-30
AR015966A1 (es) 2001-05-30
TR200001040T2 (tr) 2001-01-22
BR9814080A (pt) 2000-09-26
WO1999020280A1 (fr) 1999-04-29
CA2306985A1 (fr) 1999-04-29
HUP0003792A3 (en) 2001-12-28
CN1306426A (zh) 2001-08-01
CZ20001376A3 (cs) 2002-06-12
AU740875B2 (en) 2001-11-15

Similar Documents

Publication Publication Date Title
AU740875B2 (en) Novel use of compounds for anti-pruritic activity
WO1999047131A2 (fr) Combinaison d'un agoniste inverse alpha 5 gaba-a et inhibiteur d'acetylcholinesterase
AU2012281042B2 (en) Combination ALS therapy
JPWO2006041121A1 (ja) 慢性皮膚疾患の治療および／または予防剤
US6498173B1 (en) Synergistic combination comprising roflumilast and a pde-3 inhibitor
JPS62185014A (ja) 複合調剤薬
JPS625913A (ja) ジヒドロピリジン含有製剤
EP0345931B1 (fr) Certains mélanges PAF antagonistes/antihistamine et procédés
US6455552B1 (en) Combination of a GABAA α5 inverse agonist and a muscarinic agonist
HU183119B (en) Process for producing analgesic and tone-delivering compositions containing quinazoline derivatives and benzothiadiazol derivatives
MXPA00003775A (en) Novel use of compounds for anti-pruritic activity
JPH0411526B2 (fr)
JPS6245525A (ja) 脂質低下剤
US5334592A (en) Certain PAF antagonist antihistamine combinations and methods
JPH03215435A (ja) アルドース還元酵素阻害剤を主成分とする潰瘍治療剤
US20060079513A1 (en) Methods and compositions including methscopolamine nitrate
GB1588095A (en) Composition for the treatment of scabies
AU1563902A (en) Novel use of compounds for anti-pruritic activity
EP0338010B1 (fr) Compositions pharmaceutiques pour le traitement des maladies de la peau hyperproliferantes
JPH09500648A (ja) 置換アザスピランによるヒト免疫不全ウイルス複製の阻害法
AU5010193A (en) Methods of treating psoriasis employing substituted azaspiranes
JP2005533870A (ja) アバカビールおよびアロブジンの相乗的相互作用
JP2004026810A (ja) 鼻炎用組成物
JPH06211657A (ja) 尿酸排泄剤
JPS625923A (ja) アレルギ−性疾患治療剤

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20000508

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

AX Request for extension of the european patent

Free format text: SI PAYMENT 20000508

A4 Supplementary search report drawn up and despatched

Effective date: 20020902

AK Designated contracting states

Kind code of ref document: A4

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20040503