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WO2009081219A1 - Dérivés quinazoline utiles en tant que modulateurs d'un récepteur vanilloïde - Google Patents

Dérivés quinazoline utiles en tant que modulateurs d'un récepteur vanilloïde Download PDF

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Publication number
WO2009081219A1
WO2009081219A1 PCT/IB2007/004039 IB2007004039W WO2009081219A1 WO 2009081219 A1 WO2009081219 A1 WO 2009081219A1 IB 2007004039 W IB2007004039 W IB 2007004039W WO 2009081219 A1 WO2009081219 A1 WO 2009081219A1
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Prior art keywords
pain
subject
vanilloid receptor
derivative
derivatives
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Ceased
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PCT/IB2007/004039
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English (en)
Inventor
Laxmikant Atmaram Gharat
Jitendra Maganbhai Gajera
Neelima Khairatkar-Joshi
Vidya G. Kattige
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Ichnos Sciences SA
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Glenmark Pharmaceuticals SA
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Priority to PCT/IB2007/004039 priority Critical patent/WO2009081219A1/fr
Publication of WO2009081219A1 publication Critical patent/WO2009081219A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • the present patent application provides quinazoline derivatives, which may be used as vanilloid receptor (VR) modulators.
  • the derivatives described herein are useful for treating or preventing diseases, conditions and/or disorders mediated by VRl receptors.
  • Pain perception or nociception is mediated by the peripheral terminals of a group of specialized sensory neurons, termed "nociceptors.”
  • nociceptors A wide variety of physical and chemical stimuli induce activation of such neurons in mammals, leading to recognition of a potentially harmful stimulus. Inappropriate or excessive activation of nociceptors, however, can result in debilitating acute or chronic pain.
  • chronic pain may be classified as either nociceptive or neuropathic.
  • Nociceptive pain includes tissue injury-induced pain and inflammatory pain such as that associated with arthritis.
  • Neuropathic pain is caused by damage to the sensory nerves of the peripheral or central nervous system and is maintained by aberrant somatosensory processing.
  • VRl vanilloid receptors
  • the lipophilic vanilloid, capsaicin (8-methyl-N-vanillyl-6-nonenamides; CAP) is believed to stimulate pain pathways through the release of a variety of sensory afferent neurotransmitters via a specific cell surface capsaicin receptor, cloned as the first vanilloid receptor (VRl now known as TRPVl) (Caterina MJ, et.al, Science, 14 288 (5464), 306-13 (2000)).
  • Capsaicin is the main pungent component in hot pepper. Hot pepper has been used, for a long time, not only as a spice but also as a traditional medicine in the treatment of gastric disorders and when applied locally, for the relief of pain and inflammation.
  • CAP has a wide spectrum of biological actions, and not only exhibits effects on the cardiovascular and respiratory systems but also induces pain and irritancy on local application. CAP, however, after such induction of pain, induces desensitization, both to CAP itself and also to other noxious stimuli to stop the pain.
  • the intradermal administration of capsaicin is characterized by an initial burning or hot sensation followed by a prolonged period of analgesia.
  • the analgesic component of VRl receptor activation is thought to be mediated by a capsaicin- induced desensitization of the primary sensory afferent terminal.
  • CAP and its analogues such as olvanil, nuvanil, DA-5018, SDZ-249482, and resiniferatoxin are either used or are under development as analgesic agents or therapeutic agents for urinary incontinence or skin disorder.
  • VRl is widely expressed in non-neuronal tissues in various organ systems, and the functional roles of VRl in various systems are not properly understood at this time.
  • Increasing number of animal studies have revealed the possible involvement of VRl receptors in various pathologies and based on such information VRl is now being considered as a molecular target for various indications.
  • VRl Vanilloid Receptor
  • a vanillyl (4-hydroxy 3-methoxybenzyl) group or a functionally equivalent group This class has been widely studied and is extensively reviewed by Szallasi and Blumberg.
  • Various vanilloid agonists and antagonists have been developed for the treatment of pain. The agonists work through desensitizing the receptor while antagonists block its stimulation by (patho) physiological ligands.
  • various VR modulators have been characterized as VRl antagonists.
  • EP 462761 discloses (benzopyranyl) phenylureas and related compounds as potassium channel activators and a method of using these and other compounds having potassium channel activating activity as antiischemic and/or antiarrhythmic agents.
  • PCT Publication No. WO 2003/080578 discloses heteroaromatic ureas as vanilloid receptor (VRl) modulators, in particular antagonists, for treating pain and/or inflammation.
  • VRl vanilloid receptor
  • PCT Publication No. WO 05/007652 describes substituted quinolin-4yl-amine analogues useful in the treatment of conditions related to capsaicin receptor activation.
  • a derivative which is a compound of the formula (I) and/or a pharmaceutically-acceptable salt or a solvate or a hydrate thereof:
  • Rl is independently chosen from hydrogen, C1-C5 alkyl, or C1-C5 perfluoroalkyl.
  • a derivative which is a compound of the formula (I) and/or a pharmaceutically-acceptable salt or a solvate or a hydrate thereof, which derivative possesses inhibitory activity with respect to a VR-I receptor.
  • Various embodiments and variants are provided.
  • composition that includes one or more derivatives described herein and one or more pharmaceutically-acceptable excipients.
  • a method of inhibiting vanilloid receptor 1 in a subject by administering an effective inhibitory amount of one or more derivatives described herein to the subject.
  • a method for preventing, ameliorating or treating a vanilloid receptor mediated disease, disorder or syndrome in a subject in need thereof by administering to the subject a therapeutically effective amount of one or more derivatives described herein.
  • the term "compound” is used to denote a molecule of unique, identifiable chemical structure.
  • a compound may exist as a free species.
  • the free species form of the compound may form various salts, usually with external acids or bases.
  • the term “derivative” is used as a common term for the free species form of the compound and all its salts.
  • the claim language "a derivative, which is a free species and/or a salt of the compound of the formula [I]" is used to define a genus comprising the free species compounds of the given formula and all the salts of the compounds of the given formula.
  • pharmaceutically-acceptable salts is intended to denote salts that are suitable for use in human or animal pharmaceutical products.
  • pharmaceutically-acceptable is not intended to limit the claims to substances ("derivatives") found only outside of the body.
  • alkyl refers to a group or a substituent that includes a chain of carbon atoms.
  • the chains of carbon atoms of the alkyl groups described and claimed herein may be saturated or unsaturated, straight chain or branched, substituted or unsubstituted.
  • C1-C5 alkyl denotes an alkyl group having carbon chain with from 1 to 5 carbon atoms, inclusive, which carbon chain may be saturated or unsaturated, straight chain or branched, substituted or unsubstituted.
  • aryl denotes a carbocyclic aromatic radical derived from an aromatic hydrocarbon.
  • an "aryl” radical include phenyl, naphthyl, diphenyl, fluorophenyl, methoxyethylphenyl, difluorophenyl, benzyl, benzoyloxyphenyl, carboethoxyphenyl, acetylphenyl, ethoxyphenyl, phenoxyphenyl, hydroxyphenyl, carboxyphenyl, trifluoromethylphenyl, tolyl, xylyl, and dimethylcarbamylphenyl.
  • aryl groups of the compounds described herein may be substituted by independent replacement of 1 to 3 of the hydrogen atoms on the carbocyclic aromatic skeleton with substituents including, but not limited to, halogen, —OH, --CN, mercapto, nitro, amino, substituted amino, (Cl-C ⁇ )alkyl, (Cl-C ⁇ )alkoxy, (Cl-C ⁇ )alkylthio, (Cl-C6)alkylamino, halogenated (Cl-C ⁇ )alkyl, formyl, (Cl-C ⁇ )acyl, (Cl-C ⁇ )alkoxyacyl, and (Cl-C6)acylamido, (Cl-C5)perfluoroalkyl, (Cl-C5)perfluoroalkoxy.
  • substituents including, but not limited to, halogen, —OH, --CN, mercapto, nitro, amino, substituted amino, (Cl-C ⁇ )alkyl, (Cl-
  • heteroaryl whether used alone or as part of a substituent group, is used to denote a cyclic aromatic radical having from five to ten ring atoms of which at least one ring atom is a heteroatom, i.e., it is not a carbon atom.
  • a cyclic aromatic radical having from five to ten ring atoms of which at least one ring atom is a heteroatom, i.e., it is not a carbon atom.
  • An example is where there are from 1 to 4 heteroatoms in the ring structure selected from S, O, and N.
  • the radical may be joined to the rest of the molecule via any of the ring atoms.
  • heteroaryl groups include pyridinyl, pyridazinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, quinolyl, isoquinolyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, indolyl, benzimidazolyl, benzofuranyl, cinnolinyl, indazolyl, indolizinyl, phthalazinyl, triazinyl, isoindolyl, purinyl, oxadiazolyl, thiadiazolyl, furazanyl, benzofurazanyl, benzothiophenyl, benzotriazolyl, benzothiazolyl, benzoxazolyl, quinazolinyl,
  • heteroaryl groups of the compounds described and/or claimed herein may be substituted by independent replacement of 1 to 3 hydrogen atoms of the aromatic skeleton with substituents including, but not limited to halogen, -OH, -CN, mercapto, nitro, amino, substituted amino, (Cl-C ⁇ )alkyl, (Cl-C ⁇ )alkoxy, (Cl-C ⁇ )alkylthio, (Cl-C6)alkylamino, halogenated (Cl- C6)alkyl, formyl, (Cl-C ⁇ )acyl, (Cl-C ⁇ )alkoxyacyl, (Cl-C6)acylamido, aryl, (Cl- C5)alkylaryl, (Cl-C5)perfluoroalkyl, (C1-C5) perfluoroalkyl-aryl, and haloaryl.
  • substituents including, but not limited to halogen, -OH, -CN, mercapto, nitro,
  • haloaryl is used to denote a group comprised of an aryl group substituted with halogen atom, where aryl group is as defined above and halogen is used to denote fluorine, chlorine, bromine or iodine, an example of such group is chlorophenyl.
  • Halogen atom on aryl ring can present on ortho, meta or para position of the ring.
  • perfluoroalkylaryl is used to denote a group comprised of an aryl group substituted with perfluoroalkyl group, where aryl and perfluoroalkyl groups are as defined above. An example of such group is trifluoromethylphenyl.
  • Perfluoro group on aryl ring can present on ortho, meta or para position of the ring.
  • alkylaryl is used to denote a group comprised of an aryl radical and a carbon chain that connects the aryl radical to the rest of the molecule, for example benzyl group.
  • composition may contain one compound or a mixture of compounds.
  • pharmaceutical composition is any composition useful or potentially useful in producing physiological response in a subject to which such pharmaceutical composition is administered.
  • pharmaceutically acceptable with respect to excipients is used to define non-toxic substances generally suitable for use in human or animal pharmaceutical products.
  • modulator further refers to a compound that produces a response in a VR- 1 receptor.
  • modulators are agonists and antagonists.
  • treating or “treatment” of a state, disorder or condition includes: (1) preventing or delaying the appearance of clinical symptoms of the state, disorder or condition developing in a subject that may be afflicted with or predisposed to the state, disorder or condition but does not yet experience or display clinical or subclinical symptoms of the state, disorder or condition;
  • the benefit to a subject to be treated is either statistically significant or at least perceptible to the subject or to the physician.
  • subject includes live cells, mammals (especially humans) and other animals, such as domestic animals (e.g., household pets including cats and dogs) and non- domestic animals (such as wildlife).
  • domestic animals e.g., household pets including cats and dogs
  • non- domestic animals such as wildlife.
  • a “therapeutically effective amount” means the amount of a compound that, when administered to a subject for treating a state, disorder or condition, is sufficient to effect such treatment.
  • the “therapeutically effective amount” will vary depending on the compound, the disease and its severity and the age, weight, physical condition and responsiveness of the subject to be treated.
  • Pharmaceutically acceptable salts forming part of this invention include, for example, salts derived from inorganic bases, salts of organic bases, salts of chiral bases and salts of natural or synthetic amino acids.
  • solvates includes hydrates and other solvents of crystallization (such as alcohols).
  • the compounds of the present invention may form solvates with low molecular weight solvents by methods known in the art.
  • Rl is independently chosen from hydrogen, C1-C5 alkyl, or C1-C5 perfluoroalkyl. In one preferred variant, Rl is 3-trifiuoromethyl.
  • the compound may exist in the form of a racemic mixture or individual stereoisomers.
  • the derivatives described herein are modulators of vanilloid receptor 1 (VR-I).
  • the derivatives described herein, in particular the derivatives of compounds of the formula (I) have inhibitory activity with respect to vanilloid receptor 1. More preferably, the derivatives have VR-I inhibitory activity equal to or greater than 10% as measured in a- TRPVl assay set forth in Example 4 herein below.
  • the preferred derivatives of compounds of the formula (I) have VR-I inhibitory activity equal to or greater than 10% as measured in a TRPVl assay set forth in Example 4 herein below.
  • the vanilloid receptor mediated disease, disorder or syndrome is a pain or inflammatory disease, disorder or syndrome mediated by vanilloid receptor 1 (VRl).
  • VRl vanilloid receptor 1
  • Diseases, conditions, and/or disorders that are modulated by vanilloid receptor antagonists include, but are not limited to, migraine, arthralgia, diabetic neuropathy, neurodegeneration, neurotic skin disorder, stroke, cardiac pain arising from an ischemic myocardium, Huntington's disease, memory deficits, restricted brain function, amyotrophic lateral sclerosis (ALS), dementia, urinary bladder hypersensitiveness, urinary incontinence, vulvodynia, pruritic conditions such as uremic pruritus, irritable bowel syndrome including gastro-esophageal reflux disease, enteritis, ileitis, stomach-duodenal ulcer, inflammatory bowel disease including Crohn's disease, celiac disease, inflammatory diseases such as pancreatitis, respiratory disorders (such as allergic and non-allergic rhinitis, asthma or chronic obstructive pulmonary disease), irritation of skin, eye or mucous membrane, dermatitis, and non-specific disorders such as fervescence, reti
  • the disease, condition, and/or disorder is pain (such as acute pain, chronic pain, neuropathic pain, post-operative pain, in pain due to neuralgia (e.g. post herpetic neuralgia or trigeminal neuralgia), due to diabetic neuropathy, dental pain, and cancer pain.
  • pain such as acute pain, chronic pain, neuropathic pain, post-operative pain, in pain due to neuralgia (e.g. post herpetic neuralgia or trigeminal neuralgia), due to diabetic neuropathy, dental pain, and cancer pain.
  • VRl antagonists are useful in the treatment of inflammatory pain conditions (e.g., arthritis and osteoarthritis), diabetes, obesity, urticaria, actinic keratosis, keratocanthoma, alopecia, Meniere's disease, tinnitus, hyperacusis and anxiety disorders.
  • the derivatives described herein have vanilloid receptor antagonist (VRl) activity and are useful for the treatment or prophylaxis of certain diseases or disorders mediated or associated with the activity of vanilloid receptor, including pain, chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, osteoarthritic pain, back pain, visceral pain, cancer pain, algesia, neuralgia, migraine, neuropathies, diabetic neuropathy, sciatica, HIV-related neuropathy, post-herpetic neuralgia, fibromyalgia, nerve injury, ischaemia, neurodegeneration, stroke, post stroke pain, multiple sclerosis, respiratory diseases, asthma, cough, COPD, inflammatory disorders, oesophagitis, gastroeosophagal reflux disorder (GERD), irritable bowel syndrome, inflammatory bowel disease, pelvic hypersensitivity, urinary incontinence, cystitis, burns, psoriasis, emesis, stomach duodenal ulcer
  • the invention also provides derivatives described herein for use as an active therapeutic substance, in particular in the treatment or prophylaxis of diseases or disorders mediated or associated with the activity of vanilloid receptor.
  • derivatives of the compounds of the formula (I) or formula (II) for use in the treatment or prophylaxis of pain are also provided.
  • neuropathic pain or post-operative pain e.g. acute, chronic, neuropathic pain or post-operative pain
  • pain due to neuralgia e.g. post herpetic neuralgia, trigeminal neuralgia
  • pain due to diabetic neuropathy or dental pain e.g. in the treatment of inflammatory pain conditions e.g. arthritis, and osteoarthritis, diabetes, obesity, urticaria, actinic keratosis, keratocanthoma, alopecia, Meniere's disease, tinnitus, hyperacusis arid anxiety disorders.
  • inflammatory pain conditions e.g. arthritis, and osteoarthritis
  • diabetes obesity, urticaria, actinic keratosis, keratocanthoma, alopecia, Meniere's disease, tinnitus, hyperacusis arid anxiety disorders.
  • the derivatives described herein in pharmaceutical dosage forms may be used in the form of their pharmaceutically acceptable salts, and also may be used alone or in appropriate association, as well as in combination with other pharmaceutically active compounds.
  • composition that includes one or more derivatives of compounds of the formula (I) and/or the formula (II), and one or more pharmaceutically- acceptable excipients.
  • the pharmaceutical compositions include at least one derivative described herein and a pharmaceutically acceptable excipient (such as a pharmaceutically acceptable carrier or diluent).
  • a pharmaceutically acceptable excipient such as a pharmaceutically acceptable carrier or diluent
  • the pharmaceutical composition includes a therapeutically effective amount of the derivative described herein.
  • the derivative may be associated with a pharmaceutically acceptable excipient (such as a carrier or a diluent) or be diluted by a carrier, or enclosed within a carrier which can be in the form of a capsule, sachet, paper or other container.
  • suitable carriers include, but are not limited to, water, salt solutions, alcohols, polyethylene glycols, polyhydroxyethoxylated castor oil, peanut oil, olive oil, gelatin, lactose, terra alba, sucrose, dextrin, magnesium carbonate, sugar, cyclodextrin, amylose, magnesium stearate, talc, gelatin, agar, pectin, acacia, stearic acid or lower alkyl ethers of cellulose, silicic acid, fatty acids, fatty acid amines, fatty acid monoglycerides and diglycerides, pentaerythritol fatty acid esters, polyoxyethylene, hydroxymethylcellulose and polyvinylpyrrolidone.
  • the carrier or diluent may include a sustained release material, such as glyceryl monostearate or glyceryl distearate, alone or mixed with a wax.
  • the pharmaceutical composition may also include one or more pharmaceutically acceptable auxiliary agents, wetting agents, emulsifying agents, suspending agents, preserving agents, salts for influencing oxmetic pressure, buffers, sweetening agents, flavoring agents, colorants, or any combination of the foregoing.
  • the pharmaceutical composition of the invention may be formulated so as to provide quick, sustained, or delayed release of the active ingredient after administration to the subject by employing procedures known in the art.
  • the pharmaceutical compositions may be prepared by conventional techniques, e.g., as described in Remington: The Science and Practice of Pharmacy, 20 th Ed., 2003 (Lippincott Williams & Wilkins).
  • the active compound can be mixed with a carrier, or diluted by a carrier, or enclosed within a carrier, which may be in the form of an ampoule, capsule, sachet, paper, or other container.
  • the carrier serves as a diluent, it may be a solid, semi-solid, or liquid material that acts as a vehicle, excipient, or medium for the active compound.
  • the active compound can be adsorbed on a granular solid container, for example, in a sachet.
  • compositions may be in conventional forms, for example, capsules, tablets, aerosols, solutions, suspensions or products for topical application.
  • the route of administration may be any route which effectively transports the active compound of the invention to the appropriate or desired site of action.
  • Suitable routes of administration include, but are not limited to, oral, nasal, pulmonary, buccal, subdermal, intradermal, transdermal, parenteral, rectal, depot, subcutaneous, intravenous, intraurethral, intramuscular, intranasal, ophthalmic (such as with an ophthalmic solution) or topical (such as with a topical ointment).
  • the oral route is preferred.
  • Solid oral formulations include, but are not limited to, tablets, capsules (soft or hard gelatin), dragees (containing the active ingredient in powder or pellet form), troches and lozenges. Tablets, dragees, or capsules having talc and/or a carbohydrate carrier or binder or the like are particularly suitable for oral application. Preferable carriers for tablets, dragees, or capsules include lactose, cornstarch, and/or potato starch. A syrup or elixir can be used in cases where a sweetened vehicle can be employed.
  • Liquid formulations include, but are not limited to, syrups, emulsions, soft gelatin and sterile injectable liquids, such as aqueous or non-aqueous liquid suspensions or solutions.
  • injectable solutions or suspensions preferably aqueous solutions with the active compound dissolved in polyhydroxylated castor oil.
  • Step 1 4-chloro-7-[3-(trifluoromethyl)pyridin-2-yl]quinazoline
  • This compound was prepared by using same procedure as described in WO2007/042906.
  • Step 3 jV-(3,4-dihydrospiro[chromene-2,l'-cyclobutan]-4-yl) -7-[3-(trifluoromethyl) pyridin- 2-yl]quinazolin -4-amine
  • the compounds described herein may be tested for their activity for vanilloid receptors following procedures known to a person of ordinary skill in the art.
  • the following protocol was employed for testing compounds of the present invention. This protocol is illustrative and is not meant to limit to the scope of the present invention.
  • Example 4 Screening; for TRPVl antagonist using the 45 CaI cium uptake assay The inhibition of TRPVl receptor activation was followed as inhibition of capsaicin induced cellular uptake of radioactive calcium which represents calcium influx exclusively through the plasma membrane associated TRPVl receptor.
  • Assay buffer was composed of F-12 DMEM medium supplemented with 1.8 mM CaCl 2 (final cone.) and 0.1% Bovine serum albumin.(BSA from SIGMA)
  • Wash buffer was tyrodes solution supplemented with 0.1% BSA and 1.8 mM calcium.
  • Lysis buffer contained 50 mM Tris-HCl, pH7.5, 150 mM NaCl, 1% Triton X-100, 0.5% deoxycholate and 0.1% Sodium dodicyl sulphate (SDS, SIGMA) Method:
  • the drug / vehicle / capsaicin treated 45 Ca uptake values were normalized over basal 45 Ca value. Data was expressed as % inhibition of 45 Ca uptake by test compound with respect to maximum 45 Ca uptake induced by capsaicin alone. IC 50 value was calculated from dose response curve by nonlinear regression analysis using GraphPadPRISM software. The activity results are given in Table.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Rheumatology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pain & Pain Management (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention porte sur des dérivés quinazoline des composés représentés par la formule (I): qui peuvent être utilisés en tant que modulateurs d'un récepteur vanilloïde. On décrit également divers procédés, formulations, variants et modes de réalisation.
PCT/IB2007/004039 2007-12-20 2007-12-20 Dérivés quinazoline utiles en tant que modulateurs d'un récepteur vanilloïde Ceased WO2009081219A1 (fr)

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PCT/IB2007/004039 WO2009081219A1 (fr) 2007-12-20 2007-12-20 Dérivés quinazoline utiles en tant que modulateurs d'un récepteur vanilloïde

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PCT/IB2007/004039 WO2009081219A1 (fr) 2007-12-20 2007-12-20 Dérivés quinazoline utiles en tant que modulateurs d'un récepteur vanilloïde

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021235983A1 (fr) 2020-05-20 2021-11-25 Федеральное государственное бюджетное учреждение науки Тихоокеанский институт биоорганической химии им. Г.Б.Елякова Дальневосточного отделения Российской академии наук (ТИБОХ ДВО РАН) Moyen de prolongation d'une action analgésique

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WO2005087227A1 (fr) * 2004-03-04 2005-09-22 Neurogen Corporation Analogues quinazoline a substitution d'arylalkylamino
WO2007042906A1 (fr) * 2005-10-07 2007-04-19 Glenmark Pharmaceuticals S.A. Dérivés benzofusionnés substitués et leur utilisation en tant que ligands des récepteurs vanilloïdes
WO2007121299A2 (fr) * 2006-04-18 2007-10-25 Abbott Laboratories Antagonistes du sous-type 1 du récepteur vanilloïde (vr1) et utilisations de ceux-ci

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005087227A1 (fr) * 2004-03-04 2005-09-22 Neurogen Corporation Analogues quinazoline a substitution d'arylalkylamino
WO2007042906A1 (fr) * 2005-10-07 2007-04-19 Glenmark Pharmaceuticals S.A. Dérivés benzofusionnés substitués et leur utilisation en tant que ligands des récepteurs vanilloïdes
WO2007121299A2 (fr) * 2006-04-18 2007-10-25 Abbott Laboratories Antagonistes du sous-type 1 du récepteur vanilloïde (vr1) et utilisations de ceux-ci

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Title
GUNTHORPE MARTIN J ET AL: "Peripheral TRPV1 receptors as targets for drug development: new molecules and mechanisms.", CURRENT PHARMACEUTICAL DESIGN 2008, vol. 14, no. 1, 2008, pages 32 - 41, XP002498636, ISSN: 1873-4286 *
ZHENG ET AL: "From arylureas to biarylamides to aminoquinazolines: Discovery of a novel, potent TRPV1 antagonist", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, PERGAMON, ELSEVIER SCIENCE, GB, vol. 16, no. 19, 1 October 2006 (2006-10-01), pages 5217 - 5221, XP005611725, ISSN: 0960-894X *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021235983A1 (fr) 2020-05-20 2021-11-25 Федеральное государственное бюджетное учреждение науки Тихоокеанский институт биоорганической химии им. Г.Б.Елякова Дальневосточного отделения Российской академии наук (ТИБОХ ДВО РАН) Moyen de prolongation d'une action analgésique

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