WO2005028456A1 - Thiazole derivatives as cannabinoid receptor modulators - Google Patents
Thiazole derivatives as cannabinoid receptor modulators Download PDFInfo
- Publication number
- WO2005028456A1 WO2005028456A1 PCT/EP2004/052239 EP2004052239W WO2005028456A1 WO 2005028456 A1 WO2005028456 A1 WO 2005028456A1 EP 2004052239 W EP2004052239 W EP 2004052239W WO 2005028456 A1 WO2005028456 A1 WO 2005028456A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- group
- branched
- phenyl
- disorders
- linear
- Prior art date
Links
- 0 *c1c(*)[s]c(*)n1 Chemical compound *c1c(*)[s]c(*)n1 0.000 description 2
- PSBAIJQQABAXEF-UHFFFAOYSA-N CCCCC(C(C1)NC(c2ccccc2)=C1c(c(N)c1)ccc1N)=O Chemical compound CCCCC(C(C1)NC(c2ccccc2)=C1c(c(N)c1)ccc1N)=O PSBAIJQQABAXEF-UHFFFAOYSA-N 0.000 description 1
- CQRFTLSCLAJSGH-UHFFFAOYSA-N CCCCCc1c(-c2ccccc2)nc(C(N(CC2)CCN2C(C)C)=O)[s]1 Chemical compound CCCCCc1c(-c2ccccc2)nc(C(N(CC2)CCN2C(C)C)=O)[s]1 CQRFTLSCLAJSGH-UHFFFAOYSA-N 0.000 description 1
- VENVINVOOZALKD-UHFFFAOYSA-N CCCCCc1c(-c2ccccc2)nc(C(NC2C(CC3)CC3C2)=O)[s]1 Chemical compound CCCCCc1c(-c2ccccc2)nc(C(NC2C(CC3)CC3C2)=O)[s]1 VENVINVOOZALKD-UHFFFAOYSA-N 0.000 description 1
- KLLAXMAIBUANCQ-UHFFFAOYSA-N O=C(C1=NC(Cc2ccccc2)C(C2C=C=C=CC2)S1)NC1CCCCC1 Chemical compound O=C(C1=NC(Cc2ccccc2)C(C2C=C=C=CC2)S1)NC1CCCCC1 KLLAXMAIBUANCQ-UHFFFAOYSA-N 0.000 description 1
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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- 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
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- 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
-
- 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
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/24—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Definitions
- the present invention relates to a group of thiazole derivatives, to methods for the preparation of these compounds, to pharmaceutical compositions containing at least one these compounds as active ingredient, as well to the use of these compositions for the treatment of psychiatric and neurological disorders and other diseases involving cannabinoid CB neurotransmission.
- the thiazole derivatives of the invention are either cannabinoid (CB) receptor antagonists, CB receptor agonists, CB receptor inverse agonists or CB receptor partial agonists.
- CB cannabinoid
- the thiazole derivatives of the invention bind either on the CB 1 receptor or on the CB 2 receptor or on both the CBi and CB 2 receptor.
- the invention relates to the use of a compound disclosed herein for the manufacture of a medicament giving a beneficial effect.
- a beneficial effect is disclosed herein or apparent to a person skilled in the art from the specification and general knowledge in the art.
- the invention also relates to the use of a compound of the invention for the manufacture of a medicament for treating or preventing a disease or condition. More particularly, the invention relates to a new use for the treatment of a disease or condition disclosed herein or apparent to a person skilled in the art from the specification and general knowledge in the art.
- specific compounds disclosed herein are used for the manufacture of a medicament.
- Thiazoles have been claimed in WO0127094 as triglyceride inhibitors.
- WO0426863 describes thiazole derivatives as transforming growth factor (TgF) inhibitors.
- 4,5- Diarylthiazole derivatives have been described in EP 388909 and EP 377457 as 5- lipoxygenase inhibitors for the treatment of thrombosis, hypertension, allergy and inflammation.
- the exemplified structures therein all contain two phenyl rings which are psubstituted with a methoxy, fluoro, methylthio or methylsulfinyl group.
- WO 9603392 describes sulfonylaryl-arylthiazoles for inflammation and pain, arthritis or fever as inflammation-associated disorders.
- JP 05345772 relates to 4,5- diarylthiazoles as acetyl cholinesterase inhibitors, and JP 04154773 describes 4,5- diarylthiazoles having analgesic, anti-inflammatory and antipyretic action. It has now surprisingly been found that the thiazole derivatives of the formula (I), pro- drugs thereof and salts thereof
- R and Ri are the same or different and represent phenyl or pyridinyl, optionally substituted with 1-3 substituents Y, wherein Y represents a substituent from the group methyl, ethyl, propyl, methoxy, ethoxy, hydroxy, hydroxy methyl, hydroxyethyl, chloro, iodo, bromo, fluoro, trifluoromethyl, trifluoromethoxy, methylsulfonyl, methylsulfanyl, trifluoromethylsulfonyl, phenyl or cyano, with the proviso that X does not represent the subgroup (ii), or one of the moieties R and Ri represents a phenyl or pyridinyl group, optionally substituted with 1-3 substituents Y, wherein Y has the abovementioned meaning and frie other moiety represents a hydrogen atom or a C 1-8 branched or linear alkyl group, C 3 -
- 7 -heterocycloalkyl-C 1-3 -alkyl group contains one or two heteroatoms from the group (O, N, S), or said other moiety represents a benzyl group optionally substituted on its phenyl ring with 1-3 substituents Y, wherein Y has the abovementioned meaning, X represents one of the subgroups (i) or (ii),
- R 2 represents a C ⁇ -8 branched or linear alkyl group, C cycloalkyl group, C 3-7 - cycloalkyl-C ⁇ -2 -alkyl group, C 3 - 7 -heterocycloalkyl-C ⁇ -2 -alkyl group which groups may be substituted with a hydroxy, methyl or trifluoromethyl group or a fluoro atom and which C 3 - 7 -heterocycloalkyl-C ⁇ -2 -alkyl group contains one or two heteroatoms from the group (O, N, S), or R 2 represents a phenyl, benzyl, phenethyl or phenyl propylgroup which may be substituted on their phenyl ring with with 1-3 substituents Y, wherein Y has the abovementioned meaning, or R 2 represents a pyridyl, thienyl or naphtyl group, which napthyl group
- R 4 represents a group NR 5 R 6 wherein R 5 and Rs - together with the nitrogen atom to which they are attached -form a saturated or unsaturated, monocyclic or bicyclic, heterocyclic group having 4 to 10 ring atoms, which heterocyclic group contains one or more heteroatoms from the group (O, N, S) and which heterocyclic group may be substituted with a branched or linear C 1-3 alkyl, phenyl, hydroxy or trifluoromethyl group or a fluoro atom, or R 3 and R 4 - together with the nitrogen atom to which they are attached - form a saturated or unsatur
- prodrugs are modulators of the cannabinoid CB receptor.
- compounds having formula (I) racemates, mixtures of diastereomers and the individual steroisomers.
- prodrugs i.e. compounds which when administered to humans by any known route, are metabolised to compounds having formula (I), belong to the invention.
- Prodrugs are bioreversible derivatives of drug molecules used to overcome some barriers to the utility of the parent drug molecule. These barriers include, but are not limited to, solubility, permeability, stability, presystemic metabolism and targeting limitations (J. Stella, "Prodrugs as therapeutics", Expert Qpin.
- the compounds according to the invention are suitable for use in the treatment of psychiatric disorders such as psychosis, anxiety, depression, attention deficits, memory disorders, cognitive disorders, appetite disorders, obesity, addiction, appetence, drug dependence and neurological disorders such as neurodegenerative disorders, dementia, dystonia, muscle spasticity, tremor, epilepsy, multiple sclerosis, traumatic brain injury, stroke, Parkinson's disease, Alzheimer's disease, epilepsy, Huntington's disease, Tourette's syndrome, cerebral ischaemia, cerebral apoplexy, craniocerebral trauma, stroke, spinal cord injury, neuroinflammatory disorders, plaque sclerosis, viral encephalitis, demyelinisation related disorders, as well as for the treatment of pain disorders, including neuropathic pain disorders, and other diseases involving cannabinoid neurotransmission, including the treatment of septic shock, glaucoma, cancer, diabetes, emesis, nausea, asthma, respiratory diseases, gastrointestinal disorders, sexual disorders, gastric ulcers, diar
- the affinity of the compounds of the invention for cannabinoid CB 1 receptors can be determined using membrane preparations of Chinese hamster ovary (CHO) cells in which the human cannabinoid CB T receptor is stably transfected in conjunction with [ 3 H]CP-55,940 as radioligand. After incubation of a freshly prepared cell membrane preparation with the [ 3 H]-ligand, with or without addition of compounds of the invention, separation of bound and free ligand is performed by filtration over glassfiber filters. Radioactivity on the filter is measured by liquid scintillation counting.
- CHO Chinese hamster ovary
- the affinity of the compounds of the invention for cannabinoid CB 2 receptors can be determined using membrane preparations of Chinese hamster ovary (CHO) cells in which the human cannabinoid CB 2 receptor is stably transfected in conjunction with [ 3 H]CP-55,940 as radioligand. After incubation of a freshly prepared cell membrane preparation with the [ 3 H]-ligand, with or without addition of compounds of the invention, separation of bound and free ligand is performed by filtration over glassfiber filters. Radioactivity on the filter is measured by liquid scintillation counting.
- CHO Chinese hamster ovary
- CBi receptor antagonism can be assessed with the human CBi receptor cloned in Chinese hamster ovary (CHO) cells.
- CHO cells are grown in a Dulbecco's Modified Eagle's medium (DMEM) culture medium, supplemented with 10% heat- inactivated fetal calf serum.
- DMEM Dulbecco's Modified Eagle's medium
- Medium is aspirated and replaced by DMEM, without fetal calf serum, but containing [ 3 H]-arachidonic acid and incubated overnight in a cell culture stove (5% C0 2 /95% air; 37 Q C; water-saturated atmosphere). During this period [ 3 H]-arachidonic acid is incorporated in membrane phospholipids.
- CBi antagonism can be assessed with the CP-55,940-induced hypotension test in rat.
- Male normotensive rats 225-300 g; Harlan, Horst, The Netherlands
- pentobarbital 80 mg/kg ip
- Blood pressure is measured, via a cannula inserted into the left carotid artery, by means of a Spectramed DTX-plus pressure transducer (Spectramed B.V., Bilthoven, The Netherlands).
- the blood pressure signal is registered on a personal computer (Compaq Deskpro 386s), by means of a Po-Ne-Mah data- acquisition program (Po-Ne-Mah Inc., Storrs, USA).
- Heart rate is derived from the pulsatile pressure signal. All compounds are administered orally as a microsuspension in 1% methylcellulose 30 minutes before induction of the anesthesia which is 60 minutes prior to administration of the CBi receptor agonist CP-55,940.
- the injection volume is 10 mL kg "1 .
- This hypotension test can also be used to assess CBi receptor agonistic effects of the compounds.
- CBi agonistic effects on blood pressure may be counteracted by a selective CBi receptor antagonist such as rimonabant.
- Cannabinoid receptor agonistic or partial agonistic activity of compounds of the invention can be determined according to published methods, such as assessment of in vivo cannabimimetic effects (Wiley, J. L. et al., J Pharmacol. Exp. Ther. 2001,
- the compounds of the invention can be brought into forms suitable for administration by means of usual processes using auxiliary substances and/or liquid or solid carrier materials.
- compositions which are important and novel embodiments of the invention because of the presence of the compounds, more particularly specific compounds disclosed herein.
- Types of pharmaceutical compositions that may be used include but are not limited to tablets, chewable tablets, capsules, solutions, parenteral solutions, suppositories, suspensions, and other types disclosed herein or apparent to a person skilled in the art from the specification and general knowledge in the art.
- a pharmaceutical pack or kit is provided comprising one or more containers filled with one or more of the ingredients of a pharmaceutical composition of the invention.
- Associated with such container(s) can be various written materials such as instructions for use, or a notice in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals products, which notice reflects approval by the agency of manufacture, use, or sale for human or veterinary administration.
- Thiazole derivatives can be obtained according to methods known, for example.
- Alfahaloketones can be obtained by halogenation of the corresponding ketone.
- the reaction of alfa-halo carbonyl compounds and thioamide can produce a wide range of thiazole derivatives. More in particular, condensation of alfa-bromoketones with ethyl thiooxamate provides (2-ethoxy-carbonyl)thiazoles of general formula (II). (ll) (ill)
- a compound having formula (II) is converted into the corresponding carboxylic acid and subsequently reacted with a so-called halogenating agent such as for example thionyl chloride (SOCI 2 ).
- SOCI 2 thionyl chloride
- This reaction gives the corresponding carbonyl chloride that is subsequently reacted with a compound having formula R 3 R 4 NH wherein R 3 and R 4 have the meanings as described above.
- the ester group in (II) can be converted to the corresponding carboxylic acid.
- This carboxylic acid can be reacted with a compound having formula R3R4.NH wherein Rg and R 4 have the meanings as described hereinabove via activating and coupling methods such as formation of an active ester, or in the presence of a so- called coupling reagent, such as for example, DCC, HBTU, HOAT (N-hydroxy-7- azabenzotriazole), BOP, CIP (2-chloro-1 ,3-dimethylimidazolinium hexafluoro- phosphate), PyAOP (7-azabenzotriazol-1-yloxytris(pyrrolidino)-phosphoniurn hexa- fluorophosphate) and the like.
- a so- called coupling reagent such as for example, DCC, HBTU, HOAT (N-hydroxy-7- azabenzotriazole), BOP, CIP (2-chloro-1 ,3-dimethylimidazolinium hexafluoro- phosphat
- Part A To a solution of 1-(2,4-dichlorophenyl)-2-phenylethanone (54.35 gram, 0.205 mol) in benzene (220 mL) is slowly added bromine (10.6 mL, 0.205 mol) and the resulting solution is stirred at room temperature for 1 hour. Aqueous (5 %) NaHCO 3 solution is slowly added. The organic layer is separated, dried over MgS0 4 , filtered and evaporated in vacuo to give crude 2-bromo-1-(2,4-dichlorophenyl)-2- phenylethanone (69.4 g, 98 % yield) as an oil.
- Part D To a magnetically stirred suspension of 4-(2,4-dichlorophenyl)-5- phenylthiazole-2-carboxylic acid (4.2 g, 0.012 mol) in anhydrous dichloromethane (170 ml) is successively added 7-aza-1-hydroxybenzotriazole (HOAT) (4.083 gram, 0.030 mol), 7-azabenzotriazol-1-yloxytris(pyrrolidino)phosphonium hexafluorophos- phate (PyAOP) (15.64 gram, 0.03 mol), diisopropylethylamine (6.26 ml, 0.036 mol) and N-methoxy-N-methylamine.HCI (2.925 gram, 0.030 mol) and the resulting solution is stirred for 16 hours at room temperature.
- HOAT 7-aza-1-hydroxybenzotriazole
- PyAOP 7-azabenzotriazol-1-yloxytris
- Part E To a cooled (- 70 °C) and stirred solution of N-methyl-N-methoxy-4-(2,4- dichlorophenyl)-5-phenylthiazo!e-2-carboxamide (2.0 gram, 0.005 mol) in THF (20 ml) under 1 - is added n-BuLi (3.13 ml, 1.6 M solution in hexane, 0.005 mol). After stirring for 30 minutes the solution is allowed to attain room temperature and stirred for 16 hours. Aqueous HCI (20 ml, 1 N) is added and the resulting mixture is extracted with diethyl ether.
- Example 3 Melting point: 78-80 °C.
- Example 5 Melting point: 131-132 °C.
- Part A To a magnetically stirred solution of 1-phenylheptan-1-one (23.7 gram, 0.125 mol) in benzene (160 mL) is slowly added bromine (7.0 mL, 0.125 mol) and tie resulting solution is reacted at room temperature for 1 hour. Aqueous (5 %) NaHCO 3 solution is slowly added, followed by dichloromethane. The organic layer is separated, dried over MgS0 4 , filtered and evaporated in vacuo to give crude 2 bromo-1-phenylheptan-1-one (41.8 g, quantitative yield) as an oil.
- Part C To a magnetically stirred solution of ethyl 5(n-pentyl)-4-phenylthiazole-2- carboxylate (12.09 g, 0,039 mol) in methanol (240 ml) is slowly added a solution of KOH (8.9 g) in water (240 ml). The resulting solution is heated at reflux temperature for 2 hours and subsequently cooled to room temperature. A mixture of concentrated HCI and ice is added. The formed precipitate is collected, successively washed with water and cold diethyl ether and dried to give 5-(n-pentyl)-4-phenylthiazole-2- carboxylic acid (3.54 gram, 32 % yield).
- Part D To a magnetically stirred suspension of 5-(n-pentyl)-4-phenylthiazole-2- carboxylic acid (1.18 g, 0.0043 mol) in anhydrous dichloromethane (35 ml) is successively added 7-aza-1-hydroxybenzotriazole (HOAT) (1.46 gram, 0.0107 mol), 7-azabenzotriazol-1-yloxytris(pyrrolidino)phosphonium hexafluorophos- phate (PyAOP) (5.59 gram, 0.0107 mol), diisopropylethylamine (2.24 ml, 0.0129 mol) and aniline (0.98 ml, 0.0107 mol) and the resulting solution is stirred for 16 hours at room temperature.
- HOAT 7-aza-1-hydroxybenzotriazole
- PyAOP 7-azabenzotriazol-1-yloxytris(pyrrolidino)phosphonium hexa
- Example 7 Melting point: 90-92 °C. from 5-(n-pentyl)-4-phenylthiazole-2-carboxylic acid and cis-myrtanylamine (CAS 38235-68-6)
- Part B To a magnetically stirred solution of 1 -aminoadamantane (1.607 gram, 0.0086 mol) in anhydrous dichloromethane (10 ml) is added AI(CH 3 ) 3 (4.3 mL, 2M solution in hexane, 0.0086 mol) and the resulting solution is reacted at room temperature for 10 minutes. Aqueous (5 %) NaHC0 3 solution is slowly added.
- Example 11 Melting point: 84-85 °C. from ethyl 5-(n-pentyl)-4-phenylthiazole-2-carboxylate and exo-2-amino- bicyclo[2.2.1]heptane
- Example 12 Melting point: 64-65 °C.
- Example 13 Melting point: 80-82 °C.
- Example 14 Melting point: 84-85 °C. from ethyl 5-(n-pentyl)-4-phenylthiazole-2-carboxylate and indan-2-ylamine
- Example 16 Melting point: 86-87 °C.
- Example 17 Melting point: 50-51 °C. from ethyl 5-(n-pentyl)-4-phenylthiazole-2-carboxylate and R-(+)-bornylamine (CAS 32511-34-5).
- Example 19 Melting point: 104- 106 °C.
- Example 25 1 H-NMR (400 MHz, CDCI 3 ): 50.80 (br t, J ⁇ 7 Hz, 3H), 1.14-1.28 (m, 4H), 1.50-1.62 (m, 2H), 2.56-2.66 (m, 2H), 3.56 (br s, 3H), 6.80-7.45 (m, 8H).
- Cannabinoid receptor affinity data obtained according to the protocols given above are shown in the table below.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Diabetes (AREA)
- Pain & Pain Management (AREA)
- Pulmonology (AREA)
- Hospice & Palliative Care (AREA)
- Endocrinology (AREA)
- Ophthalmology & Optometry (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Heart & Thoracic Surgery (AREA)
- Psychology (AREA)
- Emergency Medicine (AREA)
- Reproductive Health (AREA)
- Child & Adolescent Psychology (AREA)
- Virology (AREA)
- Vascular Medicine (AREA)
Abstract
Description
Claims
Priority Applications (12)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2004274184A AU2004274184B2 (en) | 2003-09-19 | 2004-09-20 | Thiazole derivatives as cannabinoid receptor modulators |
MXPA06002061A MXPA06002061A (en) | 2003-09-19 | 2004-09-20 | Thiazole derivatives as cannabinoid receptor modulators. |
DE602004031346T DE602004031346D1 (en) | 2003-09-19 | 2004-09-20 | THIAZONE DERIVATIVES AS MODULATORS OF CANNABINOID RECEPTOR |
CA002534798A CA2534798A1 (en) | 2003-09-19 | 2004-09-20 | Thiazole derivatives as cannabinoid receptor modulators |
UAA200604048A UA83862C2 (en) | 2003-09-19 | 2004-09-20 | Thiazole derivatives as cannabinoid receptor modulators |
AT04787171T ATE497953T1 (en) | 2003-09-19 | 2004-09-20 | THIAZOLE DERIVATIVES AS MODULATORS OF THE CANNABINOID RECEPTOR |
BRPI0414514-3A BRPI0414514A (en) | 2003-09-19 | 2004-09-20 | use of a compound, compound, and pharmaceutical compositions |
EP04787171A EP1664005B1 (en) | 2003-09-19 | 2004-09-20 | Thiazole derivatives as cannabinoid receptor modulators |
JP2006526643A JP2007533621A (en) | 2003-09-19 | 2004-09-20 | Thiazole derivatives as cannabinoid receptor modulators |
IL173334A IL173334A0 (en) | 2003-09-19 | 2006-01-24 | Thiazole derivatives as cannabinoid receptor modulators |
NO20061701A NO20061701L (en) | 2003-09-19 | 2006-04-18 | Thiazole derivatives as cannabionoid receptor modulators |
HK06112654.6A HK1092143A1 (en) | 2003-09-19 | 2006-11-17 | Thiazole derivatives as cannabinoid receptor modulators |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP03078309.6 | 2003-09-19 | ||
EP03078309 | 2003-09-19 | ||
US50421203P | 2003-09-22 | 2003-09-22 | |
US60/504,212 | 2003-09-22 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2005028456A1 true WO2005028456A1 (en) | 2005-03-31 |
Family
ID=34923999
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2004/052239 WO2005028456A1 (en) | 2003-09-19 | 2004-09-20 | Thiazole derivatives as cannabinoid receptor modulators |
Country Status (18)
Country | Link |
---|---|
US (1) | US20050065189A1 (en) |
EP (1) | EP1664005B1 (en) |
JP (1) | JP2007533621A (en) |
CN (1) | CN100475796C (en) |
AR (1) | AR045651A1 (en) |
AT (1) | ATE497953T1 (en) |
AU (1) | AU2004274184B2 (en) |
BR (1) | BRPI0414514A (en) |
CA (1) | CA2534798A1 (en) |
HK (1) | HK1092143A1 (en) |
MX (1) | MXPA06002061A (en) |
NO (1) | NO20061701L (en) |
RU (1) | RU2348620C2 (en) |
SA (1) | SA04250288B1 (en) |
TW (1) | TWI336697B (en) |
UA (1) | UA83862C2 (en) |
WO (1) | WO2005028456A1 (en) |
ZA (1) | ZA200603087B (en) |
Cited By (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007064272A1 (en) * | 2005-11-29 | 2007-06-07 | Astrazeneca Ab | Benzhydryl amide derivatives as cannabinoid receptor antagonists or inverse agonists |
WO2007125048A1 (en) * | 2006-04-27 | 2007-11-08 | Solvay Pharmaceuticals Gmbh | Pharmaceutical compositions comprising cbx cannabinoid receptor modulators and potassium channel modulators |
WO2008017381A1 (en) | 2006-08-08 | 2008-02-14 | Sanofi-Aventis | Arylaminoaryl-alkyl-substituted imidazolidine-2,4-diones, processes for preparing them, medicaments comprising these compounds, and their use |
WO2009021740A2 (en) | 2007-08-15 | 2009-02-19 | Sanofis-Aventis | Substituted tetrahydronaphthalenes, process for the preparation thereof and the use thereof as medicaments |
WO2010003624A2 (en) | 2008-07-09 | 2010-01-14 | Sanofi-Aventis | Heterocyclic compounds, processes for their preparation, medicaments comprising these compounds, and the use thereof |
WO2010068601A1 (en) | 2008-12-08 | 2010-06-17 | Sanofi-Aventis | A crystalline heteroaromatic fluoroglycoside hydrate, processes for making, methods of use and pharmaceutical compositions thereof |
US7763607B2 (en) | 2006-04-27 | 2010-07-27 | Solvay Pharmaceuticals Gmbh | Pharmaceutical compositions comprising CBx cannabinoid receptor modulators and potassium channel modulators |
JP2010539145A (en) * | 2007-09-13 | 2010-12-16 | イプセン ファルマ ソシエテ パール アクシオン サンプリフィエ | 4-Phenyl-1,3-thiazole and 4-phenyl-1,3-oxazole derivatives as ligands for cannabinoid receptors |
WO2011023754A1 (en) | 2009-08-26 | 2011-03-03 | Sanofi-Aventis | Novel crystalline heteroaromatic fluoroglycoside hydrates, pharmaceuticals comprising these compounds and their use |
WO2011157827A1 (en) | 2010-06-18 | 2011-12-22 | Sanofi | Azolopyridin-3-one derivatives as inhibitors of lipases and phospholipases |
WO2012120054A1 (en) | 2011-03-08 | 2012-09-13 | Sanofi | Di- and tri-substituted oxathiazine derivates, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
WO2012120053A1 (en) | 2011-03-08 | 2012-09-13 | Sanofi | Branched oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
WO2012120052A1 (en) | 2011-03-08 | 2012-09-13 | Sanofi | Oxathiazine derivatives substituted with carbocycles or heterocycles, method for producing same, drugs containing said compounds, and use thereof |
WO2012120051A1 (en) | 2011-03-08 | 2012-09-13 | Sanofi | Benzyl-oxathiazine derivates substituted with adamantane or noradamantane, medicaments containing said compounds and use thereof |
WO2012120056A1 (en) | 2011-03-08 | 2012-09-13 | Sanofi | Tetrasubstituted oxathiazine derivatives, method for producing them, their use as medicine and drug containing said derivatives and the use thereof |
WO2012120050A1 (en) | 2011-03-08 | 2012-09-13 | Sanofi | Novel substituted phenyl-oxathiazine derivatives, method for producing them, drugs containing said compounds and the use thereof |
WO2012120058A1 (en) | 2011-03-08 | 2012-09-13 | Sanofi | Oxathiazine derivatives which are substituted with benzyl or heteromethylene groups, method for producing them, their use as medicine and drug containing said derivatives and the use thereof |
WO2012120055A1 (en) | 2011-03-08 | 2012-09-13 | Sanofi | Di- and tri-substituted oxathiazine derivates, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
WO2012120057A1 (en) | 2011-03-08 | 2012-09-13 | Sanofi | Novel substituted phenyl-oxathiazine derivatives, method for producing them, drugs containing said compounds and the use thereof |
EP2855440A1 (en) * | 2012-05-31 | 2015-04-08 | Phenex Pharmaceuticals AG | Carboxamide or sulfonamide substituted thiazoles and related derivatives as modulators for the orphan nuclear receptor ror[gamma] |
US9238027B2 (en) | 2009-01-12 | 2016-01-19 | Fundacion Del Hospital Nacional De Paraplejicos Para La Investigacion Y La Integracion (Fuhnpaiin) | Use of CB1 antagonists and/or inverse agonists for the preparation of drugs that increase motor neuron excitability |
US9597318B2 (en) | 2009-10-02 | 2017-03-21 | Avexxin As | 2-oxothiazole compounds and method of using same for chronic inflammatory disorders |
US10150781B2 (en) | 2014-08-01 | 2018-12-11 | Avexxin As | 2-oxothiatole compounds having activity as CPLA2 inhibitors for the treatment of inflammatory disorders and hyperproliferative disorders |
US10259801B2 (en) | 2013-01-29 | 2019-04-16 | Avexxin As | Anti-inflammatory and antitumor 2-oxothiazoles ABD 2-oxothiophenes compounds |
US11439625B2 (en) | 2016-03-14 | 2022-09-13 | Avexxin As | Combination therapy for proliferative diseases |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2002319627A1 (en) * | 2001-07-20 | 2003-03-03 | Merck And Co., Inc. | Substituted imidazoles as cannabinoid receptor modulators |
AR038966A1 (en) * | 2002-03-18 | 2005-02-02 | Solvay Pharm Bv | DERIVATIVES OF TIAZOL THAT HAVE ANTAGONIST, AGONIST OR PARTIAL AGONIST ACTIVITY OF CB1 |
WO2006017892A1 (en) * | 2004-08-16 | 2006-02-23 | Northern Sydney And Central Coast Area Health Service | Methods for improving cognitive functioning |
US20070254863A1 (en) * | 2006-04-27 | 2007-11-01 | Jochen Antel | Use of CBx cannabinoid receptor modulators as potassium channel modulators |
JP6434968B2 (en) | 2013-07-02 | 2018-12-05 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | Tricyclic pyrido-carboxamide derivatives as ROCK inhibitors |
US9663529B2 (en) | 2013-07-02 | 2017-05-30 | Bristol-Myers Squibb Company | Tricyclic pyrido-carboxamide derivatives as rock inhibitors |
CN104447612A (en) * | 2013-09-16 | 2015-03-25 | 天津市汉康医药生物技术有限公司 | Acotiamide hydrate crystal form and its preparation method and use |
JOP20200117A1 (en) * | 2014-10-30 | 2017-06-16 | Janssen Pharmaceutica Nv | TRIFLUOROMETHYL ALCOHOLS AS MODULATORS OF ROR?t |
CA3103770A1 (en) | 2018-06-18 | 2019-12-26 | Janssen Pharmaceutica Nv | Phenyl and pyridinyl substituted imidazoles as modulators of roryt |
WO2022128050A1 (en) | 2020-12-14 | 2022-06-23 | Symrise Ag | Medicament for fighting inflammation and pain |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2250527A1 (en) * | 1973-11-09 | 1975-06-06 | Egyt Gyogyszervegyeszeti Gyar | |
FR2261756A1 (en) * | 1974-02-27 | 1975-09-19 | Roussel Uclaf | 2-Thiazole-N-(Piperazino or piperidino) alkyl carboxamides - as hypotensive and anti-hypertensive agents of low toxicity |
EP0169502A2 (en) * | 1984-07-25 | 1986-01-29 | Merck & Co. Inc. | 2-Benzyl-4-(2-morpholino)-4-Pyriol) Thiazole |
EP0199968A1 (en) * | 1985-03-27 | 1986-11-05 | Zenyaku Kogyo Kabushiki Kaisha | Thiazole derivatives |
EP0506194A1 (en) * | 1991-03-25 | 1992-09-30 | Akzo Nobel N.V. | 4-aryl-thiazole or imidazole derivatives |
WO1994020476A1 (en) * | 1993-03-02 | 1994-09-15 | Fujisawa Pharmaceutical Co., Ltd. | Novel heterocyclic compound |
WO2001027094A1 (en) * | 1999-10-12 | 2001-04-19 | Japan Tobacco Inc. | Hypertriglyceridemia remedies and antiobestics |
WO2003007887A2 (en) * | 2001-07-20 | 2003-01-30 | Merck & Co., Inc. | Substituted imidazoles as cannabinoid receptor modulators |
WO2003078413A1 (en) * | 2002-03-18 | 2003-09-25 | Solvay Pharmaceuticals B.V. | Thiazole derivatives having cb1-antagonistic, agonistic or partial agonistic activity |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP3003148B2 (en) * | 1989-01-05 | 2000-01-24 | 藤沢薬品工業株式会社 | Thiazole compound, process for producing the same, and pharmaceutical composition containing the same |
US5217971A (en) * | 1989-01-05 | 1993-06-08 | Fujisawa Pharmaceutical Co., Ltd. | Thiazole compounds and pharmaceutical composition comprising the same |
CA2012716A1 (en) * | 1989-03-22 | 1990-09-22 | Akito Tanaka | Thiazole compounds, processes for the preparation thereof and pharmaceutical composition comprising the same |
GB9204958D0 (en) * | 1992-03-06 | 1992-04-22 | Fujisawa Pharmaceutical Co | Thiazole derivatives |
CA2195847A1 (en) * | 1994-07-27 | 1996-02-08 | John J. Talley | Substituted thiazoles for the treatment of inflammation |
WO2001058869A2 (en) * | 2000-02-11 | 2001-08-16 | Bristol-Myers Squibb Company | Cannabinoid receptor modulators, their processes of preparation, and use of cannabinoid receptor modulators in treating respiratory and non-respiratory diseases |
JP2002302488A (en) * | 2000-03-30 | 2002-10-18 | Takeda Chem Ind Ltd | Substituted 1,3-thiazole compound, its production method and use thereof |
AU2001282875A1 (en) * | 2000-08-21 | 2002-03-04 | Pharmacia And Upjohn Company | Quinuclidine-substituted heteroaryl moieties for treatment of disease |
AU2001284646A1 (en) * | 2000-08-21 | 2002-03-04 | Pharmacia And Upjohn Company | Quinuclidine-substituted heteroaryl moieties for treatment of disease |
FR2827916B1 (en) * | 2001-07-25 | 2003-10-31 | Inst Francais Du Petrole | METHOD FOR CONTROLLING THE IGNITION PARAMETERS OF A SPARK PLUG FOR AN INTERNAL COMBUSTION ENGINE AND IGNITION DEVICE USING SUCH A METHOD |
EP1419161A1 (en) * | 2001-08-24 | 2004-05-19 | PHARMACIA & UPJOHN COMPANY | Substituted-heteroaryl-7-aza 2.2.1]bicycloheptanes for the treatment of disease |
BR0214031A (en) * | 2001-11-08 | 2004-10-19 | Upjohn Co | Substituted azabicyclic heteroaryl compounds for the treatment of disease |
EP1461022A2 (en) * | 2001-12-17 | 2004-09-29 | ALTANA Pharma AG | Use of selective pde5 inhibitors for treating partial and global respiratory failure |
-
2004
- 2004-09-15 TW TW093127874A patent/TWI336697B/en not_active IP Right Cessation
- 2004-09-15 SA SA4250288A patent/SA04250288B1/en unknown
- 2004-09-15 AR ARP040103290A patent/AR045651A1/en not_active Application Discontinuation
- 2004-09-16 US US10/942,021 patent/US20050065189A1/en not_active Abandoned
- 2004-09-20 MX MXPA06002061A patent/MXPA06002061A/en unknown
- 2004-09-20 AT AT04787171T patent/ATE497953T1/en not_active IP Right Cessation
- 2004-09-20 WO PCT/EP2004/052239 patent/WO2005028456A1/en active Application Filing
- 2004-09-20 RU RU2006113126/04A patent/RU2348620C2/en not_active IP Right Cessation
- 2004-09-20 UA UAA200604048A patent/UA83862C2/en unknown
- 2004-09-20 CN CNB2004800241125A patent/CN100475796C/en not_active Expired - Fee Related
- 2004-09-20 JP JP2006526643A patent/JP2007533621A/en active Pending
- 2004-09-20 BR BRPI0414514-3A patent/BRPI0414514A/en not_active IP Right Cessation
- 2004-09-20 CA CA002534798A patent/CA2534798A1/en not_active Abandoned
- 2004-09-20 EP EP04787171A patent/EP1664005B1/en active Active
- 2004-09-20 AU AU2004274184A patent/AU2004274184B2/en not_active Ceased
-
2006
- 2006-04-18 ZA ZA200603087A patent/ZA200603087B/en unknown
- 2006-04-18 NO NO20061701A patent/NO20061701L/en not_active Application Discontinuation
- 2006-11-17 HK HK06112654.6A patent/HK1092143A1/en not_active IP Right Cessation
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2250527A1 (en) * | 1973-11-09 | 1975-06-06 | Egyt Gyogyszervegyeszeti Gyar | |
FR2261756A1 (en) * | 1974-02-27 | 1975-09-19 | Roussel Uclaf | 2-Thiazole-N-(Piperazino or piperidino) alkyl carboxamides - as hypotensive and anti-hypertensive agents of low toxicity |
EP0169502A2 (en) * | 1984-07-25 | 1986-01-29 | Merck & Co. Inc. | 2-Benzyl-4-(2-morpholino)-4-Pyriol) Thiazole |
EP0199968A1 (en) * | 1985-03-27 | 1986-11-05 | Zenyaku Kogyo Kabushiki Kaisha | Thiazole derivatives |
EP0506194A1 (en) * | 1991-03-25 | 1992-09-30 | Akzo Nobel N.V. | 4-aryl-thiazole or imidazole derivatives |
WO1994020476A1 (en) * | 1993-03-02 | 1994-09-15 | Fujisawa Pharmaceutical Co., Ltd. | Novel heterocyclic compound |
WO2001027094A1 (en) * | 1999-10-12 | 2001-04-19 | Japan Tobacco Inc. | Hypertriglyceridemia remedies and antiobestics |
WO2003007887A2 (en) * | 2001-07-20 | 2003-01-30 | Merck & Co., Inc. | Substituted imidazoles as cannabinoid receptor modulators |
WO2003078413A1 (en) * | 2002-03-18 | 2003-09-25 | Solvay Pharmaceuticals B.V. | Thiazole derivatives having cb1-antagonistic, agonistic or partial agonistic activity |
Non-Patent Citations (3)
Title |
---|
DATABASE CAPLUS CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; XP002313045, retrieved from STN Database accession no. 1995:248274 * |
KULKARNI R A ET AL: "2-Benzoyl-4-substituted-phenyl- 5-phenylthiazoles", JOURNAL OF THE INDIAN CHEMICAL SOCIETY, vol. 65, June 1988 (1988-06-01), pages 427 - 428, XP008027244 * |
OHKUBO M ET AL: "Studies on cerebral protective agents. VIII. Synthesis of 2-aminothiazoles and 2-thiazolecarboxamides with anti-anoxic activity", CHEMICAL AND PHARMACEUTICAL BULLETIN, vol. 43, no. 9, September 1995 (1995-09-01), pages 1497 - 1504, XP002313044 * |
Cited By (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007064272A1 (en) * | 2005-11-29 | 2007-06-07 | Astrazeneca Ab | Benzhydryl amide derivatives as cannabinoid receptor antagonists or inverse agonists |
WO2007125048A1 (en) * | 2006-04-27 | 2007-11-08 | Solvay Pharmaceuticals Gmbh | Pharmaceutical compositions comprising cbx cannabinoid receptor modulators and potassium channel modulators |
US7763607B2 (en) | 2006-04-27 | 2010-07-27 | Solvay Pharmaceuticals Gmbh | Pharmaceutical compositions comprising CBx cannabinoid receptor modulators and potassium channel modulators |
WO2008017381A1 (en) | 2006-08-08 | 2008-02-14 | Sanofi-Aventis | Arylaminoaryl-alkyl-substituted imidazolidine-2,4-diones, processes for preparing them, medicaments comprising these compounds, and their use |
WO2009021740A2 (en) | 2007-08-15 | 2009-02-19 | Sanofis-Aventis | Substituted tetrahydronaphthalenes, process for the preparation thereof and the use thereof as medicaments |
JP2010539145A (en) * | 2007-09-13 | 2010-12-16 | イプセン ファルマ ソシエテ パール アクシオン サンプリフィエ | 4-Phenyl-1,3-thiazole and 4-phenyl-1,3-oxazole derivatives as ligands for cannabinoid receptors |
WO2010003624A2 (en) | 2008-07-09 | 2010-01-14 | Sanofi-Aventis | Heterocyclic compounds, processes for their preparation, medicaments comprising these compounds, and the use thereof |
WO2010068601A1 (en) | 2008-12-08 | 2010-06-17 | Sanofi-Aventis | A crystalline heteroaromatic fluoroglycoside hydrate, processes for making, methods of use and pharmaceutical compositions thereof |
US9592237B2 (en) | 2009-01-12 | 2017-03-14 | Fundacion Del Hospital Nacional De Paraplejicos Para La Investigacion Y La Integracion (Fuhnpaiin) | Use of CB1 antagonists and/or inverse agonists for the preparation of drugs that increase motor neuron excitability |
US9238027B2 (en) | 2009-01-12 | 2016-01-19 | Fundacion Del Hospital Nacional De Paraplejicos Para La Investigacion Y La Integracion (Fuhnpaiin) | Use of CB1 antagonists and/or inverse agonists for the preparation of drugs that increase motor neuron excitability |
WO2011023754A1 (en) | 2009-08-26 | 2011-03-03 | Sanofi-Aventis | Novel crystalline heteroaromatic fluoroglycoside hydrates, pharmaceuticals comprising these compounds and their use |
US10370344B2 (en) | 2009-10-02 | 2019-08-06 | Avexxin As | 2-oxothiazole compounds and method of using same for chronic inflammatory disorders |
US9597318B2 (en) | 2009-10-02 | 2017-03-21 | Avexxin As | 2-oxothiazole compounds and method of using same for chronic inflammatory disorders |
WO2011157827A1 (en) | 2010-06-18 | 2011-12-22 | Sanofi | Azolopyridin-3-one derivatives as inhibitors of lipases and phospholipases |
WO2012120050A1 (en) | 2011-03-08 | 2012-09-13 | Sanofi | Novel substituted phenyl-oxathiazine derivatives, method for producing them, drugs containing said compounds and the use thereof |
WO2012120056A1 (en) | 2011-03-08 | 2012-09-13 | Sanofi | Tetrasubstituted oxathiazine derivatives, method for producing them, their use as medicine and drug containing said derivatives and the use thereof |
WO2012120058A1 (en) | 2011-03-08 | 2012-09-13 | Sanofi | Oxathiazine derivatives which are substituted with benzyl or heteromethylene groups, method for producing them, their use as medicine and drug containing said derivatives and the use thereof |
WO2012120055A1 (en) | 2011-03-08 | 2012-09-13 | Sanofi | Di- and tri-substituted oxathiazine derivates, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
WO2012120057A1 (en) | 2011-03-08 | 2012-09-13 | Sanofi | Novel substituted phenyl-oxathiazine derivatives, method for producing them, drugs containing said compounds and the use thereof |
WO2012120051A1 (en) | 2011-03-08 | 2012-09-13 | Sanofi | Benzyl-oxathiazine derivates substituted with adamantane or noradamantane, medicaments containing said compounds and use thereof |
WO2012120052A1 (en) | 2011-03-08 | 2012-09-13 | Sanofi | Oxathiazine derivatives substituted with carbocycles or heterocycles, method for producing same, drugs containing said compounds, and use thereof |
WO2012120053A1 (en) | 2011-03-08 | 2012-09-13 | Sanofi | Branched oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
WO2012120054A1 (en) | 2011-03-08 | 2012-09-13 | Sanofi | Di- and tri-substituted oxathiazine derivates, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
EP2855440A1 (en) * | 2012-05-31 | 2015-04-08 | Phenex Pharmaceuticals AG | Carboxamide or sulfonamide substituted thiazoles and related derivatives as modulators for the orphan nuclear receptor ror[gamma] |
US10301272B2 (en) | 2012-05-31 | 2019-05-28 | Phenex Pharmaceuticals Ag | Carboxamide or sulfonamide substituted thiazoles and related derivatives as modulators for the orphan nuclear receptor ROR[γ] |
US10259801B2 (en) | 2013-01-29 | 2019-04-16 | Avexxin As | Anti-inflammatory and antitumor 2-oxothiazoles ABD 2-oxothiophenes compounds |
US11034666B2 (en) | 2013-01-29 | 2021-06-15 | Avexxin As | Anti-inflammatory and antitumor 2-oxothiazoles and 2-oxothiophenes compounds |
US11691959B2 (en) | 2013-01-29 | 2023-07-04 | Avexxin As | Anti-inflammatory and antitumor 2-oxothiazoles and 2-oxothiophenes compounds |
US10150781B2 (en) | 2014-08-01 | 2018-12-11 | Avexxin As | 2-oxothiatole compounds having activity as CPLA2 inhibitors for the treatment of inflammatory disorders and hyperproliferative disorders |
US10851114B2 (en) | 2014-08-01 | 2020-12-01 | Avexxin As | 2-oxothiatole compounds having activity as cPLA2 inhibitors for the treatment of inflammatory disorders and hyperproliferative disorders |
US11439625B2 (en) | 2016-03-14 | 2022-09-13 | Avexxin As | Combination therapy for proliferative diseases |
Also Published As
Publication number | Publication date |
---|---|
US20050065189A1 (en) | 2005-03-24 |
UA83862C2 (en) | 2008-08-26 |
EP1664005B1 (en) | 2011-02-09 |
HK1092143A1 (en) | 2007-02-02 |
BRPI0414514A (en) | 2006-11-07 |
SA04250288B1 (en) | 2008-07-19 |
RU2348620C2 (en) | 2009-03-10 |
CA2534798A1 (en) | 2005-03-31 |
TWI336697B (en) | 2011-02-01 |
RU2006113126A (en) | 2007-10-27 |
CN100475796C (en) | 2009-04-08 |
NO20061701L (en) | 2006-06-16 |
SA04250288A (en) | 2005-12-03 |
CN1849310A (en) | 2006-10-18 |
AU2004274184A1 (en) | 2005-03-31 |
JP2007533621A (en) | 2007-11-22 |
AR045651A1 (en) | 2005-11-02 |
MXPA06002061A (en) | 2006-05-19 |
ATE497953T1 (en) | 2011-02-15 |
TW200517388A (en) | 2005-06-01 |
ZA200603087B (en) | 2007-09-26 |
AU2004274184B2 (en) | 2009-09-17 |
EP1664005A1 (en) | 2006-06-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1664005B1 (en) | Thiazole derivatives as cannabinoid receptor modulators | |
AU2003299024B2 (en) | 1H-1,2,4-triazole-3-carboxamide derivatives as cannabinoid-CB1 receptor ligands | |
EP1713475B1 (en) | 1,3,5-trisubstituted 4,5-dihydro-1h-pyrazole derivatives having cb1-antagonistic activity | |
CA2462692C (en) | Thiazole derivatives having cb1-antagonistic, agonistic or partial agonistic activity | |
EP1725536B1 (en) | Imidazoline derivatives having cb1-antagonistic activity | |
AU2006224853B2 (en) | Trifluoromethylbenzamide derivatives and therapeutic uses thereof | |
US7745476B2 (en) | 1,3,5-trisubstituted 4,5-dihydro-1H-pyrazole derivatives having CB1-antagonistic activity | |
KR20060117952A (en) | 1h-imidazole derivatives as cannabinoid receptor modulators | |
US7173044B2 (en) | Imidazoline derivatives having CB1-antagonistic activity | |
KR20060076780A (en) | Thiazole derivatives as cannabinoid receptor modulators |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 200480024112.5 Country of ref document: CN |
|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BW BY BZ CA CH CN CO CR CU CZ DK DM DZ EC EE EG ES FI GB GD GE GM HR HU ID IL IN IS JP KE KG KP KZ LC LK LR LS LT LU LV MA MD MK MN MW MX MZ NA NI NO NZ PG PH PL PT RO RU SC SD SE SG SK SY TJ TM TN TR TT TZ UA UG US UZ VN YU ZA ZM |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GM KE LS MW MZ NA SD SZ TZ UG ZM ZW AM AZ BY KG MD RU TJ TM AT BE BG CH CY DE DK EE ES FI FR GB GR HU IE IT MC NL PL PT RO SE SI SK TR BF CF CG CI CM GA GN GQ GW ML MR SN TD TG |
|
DPEN | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed from 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
ENP | Entry into the national phase |
Ref document number: 2534798 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 12006500274 Country of ref document: PH |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2004787171 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2004274184 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: PA/a/2006/002061 Country of ref document: MX |
|
ENP | Entry into the national phase |
Ref document number: 2004274184 Country of ref document: AU Date of ref document: 20040920 Kind code of ref document: A |
|
WWP | Wipo information: published in national office |
Ref document number: 2004274184 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2006526643 Country of ref document: JP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1020067005393 Country of ref document: KR Ref document number: 941/CHENP/2006 Country of ref document: IN |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2006/03087 Country of ref document: ZA Ref document number: 200603087 Country of ref document: ZA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2006113126 Country of ref document: RU |
|
WWP | Wipo information: published in national office |
Ref document number: 2004787171 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 1020067005393 Country of ref document: KR |
|
ENP | Entry into the national phase |
Ref document number: PI0414514 Country of ref document: BR |