WO2009095726A1 - Dérivés d'acrylamide en tant que modulateurs du récepteur vanilloïde de type 1 - Google Patents

Dérivés d'acrylamide en tant que modulateurs du récepteur vanilloïde de type 1 Download PDF

Info

Publication number
WO2009095726A1
WO2009095726A1 PCT/IB2008/000192 IB2008000192W WO2009095726A1 WO 2009095726 A1 WO2009095726 A1 WO 2009095726A1 IB 2008000192 W IB2008000192 W IB 2008000192W WO 2009095726 A1 WO2009095726 A1 WO 2009095726A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
cyclobutan
dihydrospiro
chromene
fluoro
Prior art date
Application number
PCT/IB2008/000192
Other languages
English (en)
Inventor
Laxmikant Atmaram Gharat
Jitendra Maganbhai Gajera
Neelima Khairatkar-Joshi
Vidya G. Kattigf
Original Assignee
Glenmark Pharmaceuticals, 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 Glenmark Pharmaceuticals, S.A. filed Critical Glenmark Pharmaceuticals, S.A.
Priority to PCT/IB2008/000192 priority Critical patent/WO2009095726A1/fr
Publication of WO2009095726A1 publication Critical patent/WO2009095726A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/96—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings spiro-condensed with carbocyclic rings or ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • 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
    • C07D405/02—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 two hetero rings
    • C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present patent application provides acrylamide derivatives, which may be used as vanilloid receptor- 1 (VRl) 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, H 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 i ⁇ tancy 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-
  • 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.
  • 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:
  • R 1 is selected from hydrogen or fluoro
  • R 2 is selected from pyridyl, furyl, thienyl, quinolinyl, or optionally substituted phenyl wherein substituents are chloro, methoxy or trifluoromethyl.
  • 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 1 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.
  • 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.
  • 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.
  • the use of the term “and/or” is intended to indicate that, for a compound of a given chemical structure, a claim to a “derivative" covers the free species form and all of its salts, as well as the mixtures of free species and the salt forms.
  • compositions 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:
  • 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.
  • Compounds described herein may have one or more asymmetric carbon atoms and thus may occur as racemic mixtures, enantiomers and diastereomers. These compounds may also exist as conformers/rotamers. All such isomeric forms of these compounds are expressly included in the present invention.
  • 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 14 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 14 herein below.
  • the vanilloid receptor 1 mediated disease, disorder or syndrome is a pain or inflammatory disease, disorder or syndrome.
  • Diseases, conditions, and/or disorders that are modulated by vanilloid receptor 1 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,
  • 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 1 , 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 duoden
  • 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- 1.
  • derivatives of the compounds of the formula (I) or formula (H) 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 and anxiety disorders.
  • 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 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.
  • the compounds of the formula (I) may be prepared in any suitable manner.
  • the compound of the formula (I) may be prepared by coupling of the intermediate of the formula (III) with carboxylic acid derivative of the formula (IV):
  • the scheme below describes preparation of compounds of the formula
  • This compound was prepared as per the procedure given in example 1, using 4-methoxy phenyl acrylic acid (1.0 equiv, from Aldrich) and intermediate 1 (1.0 equiv.) to get compound as a white solid.
  • IR (KBr): 3268, 3061, 2936, 1653, 1625, 1543, 1486, 1427, 1340, 1253, 1221, 1203, 1124, 1078, 998,971,819,759cm 1 .
  • This compound was prepared as per the procedure given in example 1 , using 4-chloro phenyl acrylic acid (1.0 equiv, form Aldrich) and intermediate 2 (1.0 equiv) to get compound as a white solid.
  • This compound was prepared by the method described by Sinisterra, J.V. et al., Synthesis,
  • Step 2 (2E)-N-3,4-dihydrospiro[chromene-2,r-cyclobutan]-4-yl-3-(2-furyl) acryl amide
  • This compound was prepared as per the procedure given in step 1 example, using furyl acrylic acid (1.0 equiv) and intermediate 2 (1.0 equiv)to get compound as off white solid.
  • This compound was prepared as per the procedure given in step 1 example, using 4-(Trifluoromethyl) phenyl acrylic acid (1.0 equiv.; Aldrich) and intermediate 1 (1.0 equiv) to get compound as a white solid.
  • This compound was prepared by the method described by Panizzon, L., HeIv. Chim. Acta,
  • Step 2 (2E)-N -3,4-dihydrospiro[chromene-2,l'-cyclobutan]-4-yl-3-pyridin-3-yl acrylamide
  • This compound was prepared as per the procedure given in example 1, using 3-pyridinyl acrylic acid (1.0 equiv) and intermediatel (1.0 equiv) to get compound as off white solid.
  • This compound was prepared by the method described by Tinnemans, A.H.A. et al., J.O.C.,
  • This compound was prepared as per the procedure given in step 1 example, using 2-thienyl acrylic acid (1.0 equiv) and intermediate 1 (1.0 equiv) to get compound as a off white solid.
  • This compound was prepared as per the procedure given in example 1 using 4-methoxy phenyl acrylic acid (1.0 equiv from Aldrich) and intermediate 2 (1.0 equiv) to get compound as white solid.
  • This compound was prepared as per the procedure given in example 1 using 4-chloro phenyl acrylic acid (1.0 equiv from Aldrich) and intermediate 2 (1.0 equiv) to get compound as a white solid.
  • This compound was prepared as per the procedure given in step 1 example using 2,3- dimethoxycinnamic acid (1.0 equiv from Aldrich) and intermediate 2 (1.0 equiv) to get compound as white solid.
  • This compound was prepared as per the procedure given in example 1, using 3-pyridinyl acrylic acid (1.0 equiv) and intermediate 2 (1.0 equiv) to get compound as off white solid.
  • the compounds described herein may be tested for their activity for vanilloid receptor 1 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.
  • 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-IOO, 0.5% deoxycholate and 0.1% Sodium dodicyl sulphate (SDS 5 SIGMA ) Method:
  • Radioactivity in samples was measured as counts per minute (cpm) using Packard Biosciences Top Count.
  • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Neurology (AREA)
  • Engineering & Computer Science (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 concerne des dérivés de cyanamide des composés représentés par la formule (I) : qui peuvent être utilisés en tant que modulateurs du récepteur vanilloïde de type 1. L'invention concerne également diverses méthodes, formulations, variantes et modes de réalisation apparentés.
PCT/IB2008/000192 2008-01-29 2008-01-29 Dérivés d'acrylamide en tant que modulateurs du récepteur vanilloïde de type 1 WO2009095726A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/IB2008/000192 WO2009095726A1 (fr) 2008-01-29 2008-01-29 Dérivés d'acrylamide en tant que modulateurs du récepteur vanilloïde de type 1

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IB2008/000192 WO2009095726A1 (fr) 2008-01-29 2008-01-29 Dérivés d'acrylamide en tant que modulateurs du récepteur vanilloïde de type 1

Publications (1)

Publication Number Publication Date
WO2009095726A1 true WO2009095726A1 (fr) 2009-08-06

Family

ID=39798055

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2008/000192 WO2009095726A1 (fr) 2008-01-29 2008-01-29 Dérivés d'acrylamide en tant que modulateurs du récepteur vanilloïde de type 1

Country Status (1)

Country Link
WO (1) WO2009095726A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012139963A1 (fr) * 2011-04-11 2012-10-18 Glaxo Group Limited N-cyclobutyl-imidazopyridine-méthylamine à titre d'antagoniste des trpv1
CN104083554A (zh) * 2014-07-17 2014-10-08 陈筠 一种治疗外阴瘙痒的中药组合物
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

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0126367A1 (fr) * 1983-05-18 1984-11-28 Beecham Group Plc Dérivés de chromane et chromène
EP0462761A2 (fr) * 1990-06-18 1991-12-27 E.R. SQUIBB & SONS, INC. Dérivés de benzopyranne et leurs analogues hétérocycliques comme agents anti-ischémiques
WO2006065484A2 (fr) * 2004-11-24 2006-06-22 Abbott Laboratories Composes de chromanyluree inhibant le recepteur du sous-type 1 du recepteur de vanilloide et leurs utilisations
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 (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0126367A1 (fr) * 1983-05-18 1984-11-28 Beecham Group Plc Dérivés de chromane et chromène
EP0462761A2 (fr) * 1990-06-18 1991-12-27 E.R. SQUIBB & SONS, INC. Dérivés de benzopyranne et leurs analogues hétérocycliques comme agents anti-ischémiques
WO2006065484A2 (fr) * 2004-11-24 2006-06-22 Abbott Laboratories Composes de chromanyluree inhibant le recepteur du sous-type 1 du recepteur de vanilloide et leurs utilisations
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

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012139963A1 (fr) * 2011-04-11 2012-10-18 Glaxo Group Limited N-cyclobutyl-imidazopyridine-méthylamine à titre d'antagoniste des trpv1
US8754101B2 (en) 2011-04-11 2014-06-17 Glaxo Group Limited N-cyclobutyl-imidazopyridine-methylamine as TRPV1 antagonists
CN104083554A (zh) * 2014-07-17 2014-10-08 陈筠 一种治疗外阴瘙痒的中药组合物
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

Similar Documents

Publication Publication Date Title
US7842703B2 (en) Substituted benzofused derivatives and their use as vanilloid receptor ligands
ES2219319T3 (es) Derivados de amida.
AU2010323175B2 (en) Morpholinothiazoles as alpha 7 positive allosteric modulators
JP4833069B2 (ja) テトラヒドロ−ナフタレンおよび尿素誘導体
JP4696069B2 (ja) Ｎ−［ヘテロアリル（ピペリジン−２−イル）メチル］ベンズアミドの誘導体、この調製方法およびこの治療法における使用
JP5617919B2 (ja) テトラヒドロベンゾチオフェン化合物
JP5148636B2 (ja) オレキシンアンタゴニストとしてのマロンアミド
WO2009010824A1 (fr) Ligands des récepteurs vanilloïdes
WO2006006741A1 (fr) Composé benzamide fusionné et inhibiteur d'activité récepteur vanilloïde 1 (vr1)
CN101550114A (zh) 具有cb1拮抗、激动或部分激动活性的噻唑衍生物
MXPA05003632A (es) Derivados de piperidina 1, 4-disustituidos y su uso como inhibidores de 11-beta-hidroesteroide deshidrogenasa humana de tipo 1 (11betahsd1).
BRPI0307351B1 (pt) composto, composição farmacêutica, uso de um composto, e, processo para preparar um composto
WO2008059339A2 (fr) Dérivés d'isoquinoline comme modulateurs des récepteurs vanilloïdes
CN106661043B (zh) 2-氧杂-5-氮杂双环[2.2.1]庚-3-基衍生物
CN106414438B (zh) 2-酰氨基噻唑衍生物或其盐
JP2007516256A (ja) オピオイド受容体拮抗物質
WO2008010061A2 (fr) 3-azabicyclo[3.1.0]hexanes ligands du récepteur vanilloïde, compositions pharmaceutiques les contenant et leurs procédés de préparation
BRPI0619540A2 (pt) compostos de quinazolinona, seu uso, composição farmacêutica que os compreende e processo para a produção de um composto
CA2884922A1 (fr) Derives de n-prop-2-ynyl-carboxamide et leur utilisation a titre d'antagonistes de trpa1
Thorat et al. 2-(3-Fluoro-4-methylsulfonylaminophenyl) propanamides as potent TRPV1 antagonists: Structure activity relationships of the 2-oxy pyridine C-region
WO2009095726A1 (fr) Dérivés d'acrylamide en tant que modulateurs du récepteur vanilloïde de type 1
JP2022065012A (ja) Ｄ－アミノ酸オキシダーゼ（ｄａａｏ）阻害剤としての新規な置換ベンゾイミダゾール誘導体
US8492568B2 (en) Chromane derivatives as TRPV3 modulators
WO2009034433A2 (fr) Dérivés de 3-azabicyclo [3.1.0] hexane utilisés comme ligands des récepteurs vanilloïdes
WO2005051381A1 (fr) Uree-octahydroindoles substitues utilises en tant qu'antagonistes du recepteur 1 de l'hormone concentrant la melanine (mch1r)

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 08709732

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 08709732

Country of ref document: EP

Kind code of ref document: A1