JP4667384B2 - イオンチャネルリガンドとしてのアミド誘導体および薬学的組成物、ならびにこれらを使用する方法 - Google Patents
イオンチャネルリガンドとしてのアミド誘導体および薬学的組成物、ならびにこれらを使用する方法 Download PDFInfo
- Publication number
- JP4667384B2 JP4667384B2 JP2006534356A JP2006534356A JP4667384B2 JP 4667384 B2 JP4667384 B2 JP 4667384B2 JP 2006534356 A JP2006534356 A JP 2006534356A JP 2006534356 A JP2006534356 A JP 2006534356A JP 4667384 B2 JP4667384 B2 JP 4667384B2
- Authority
- JP
- Japan
- Prior art keywords
- substituted
- unsubstituted
- compound
- alkyl
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
- C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
- C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D319/18—Ethylenedioxybenzenes, not substituted on the hetero ring
-
- 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
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/16—Central respiratory analeptics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- 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
- A61P17/06—Antipsoriatics
-
- 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
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/06—Antimigraine agents
-
- 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
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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
- A61P27/16—Otologicals
-
- 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]
-
- 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
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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
-
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/622—Forming processes; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/626—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B
- C04B35/63—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
- C04B35/632—Organic additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/65—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/66—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/67—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
- C07C233/68—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/69—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom of an acyclic saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/67—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
- C07C233/68—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/73—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/67—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
- C07C233/75—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/58—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton
- C07C255/60—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton at least one of the singly-bound nitrogen atoms being acylated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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 with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/337—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
- C07D209/16—Tryptamines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/82—Carbazoles; Hydrogenated carbazoles
- C07D209/88—Carbazoles; Hydrogenated carbazoles 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 carbon atoms of the ring system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/40—Acylated substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/53—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/56—Amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/70—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/38—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/10—Aza-phenanthrenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/10—Aza-phenanthrenes
- C07D221/12—Phenanthridines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/14—Aza-phenalenes, e.g. 1,8-naphthalimide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole 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
- C07D231/38—Nitrogen atoms
- C07D231/40—Acylated on said nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D233/61—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms not forming part of a nitro radical, attached to ring nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- 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
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
- C07D277/46—Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/14—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/58—Radicals substituted by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
- C07D319/12—1,4-Dioxanes; Hydrogenated 1,4-dioxanes not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D405/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
Description
本発明は、新規化合物およびこのような化合物を含む薬学的組成物に関する。本発明はまた、本発明の化合物および薬学的組成物を使用して、哺乳動物における疼痛関連状態および炎症関連状態(例えば、関節炎、パーキンソン病、アルツハイマー病、発作、ブドウ膜炎、喘息、心筋梗塞、疼痛症候群(急性および慢性、またはニューロパシー性)の処置および予防、外傷性脳損傷、急性脊髄損傷、神経変性障害、脱毛症(毛髪損失)、炎症性腸疾患および免疫障害(しかし、これらに限定されない))を予防および/または処置するための方法に関する。
体内のシグナル伝達経路の研究は、イオンチャネルの存在を解き明かし、そしてこれらの役割を説明しようとしてきた。イオンチャネルは、異なる2つの特徴を有する膜一体型タンパク質である:これらイオンチャネルは、膜電位または化学的リガンドの直接結合のような特異的信号によってゲート操作され(gate)(開き、そして閉じる)、そして一旦開くと、これらイオンチャネルは細胞膜を横切って非常に高速でイオンを導く。
ここで、本明細書中に記載される化合物のような化合物が、哺乳動物のイオンチャネル(例えば、VR1カチオンチャネル)を変更し得ることが見出された。この知見は、治療上価値を有する新規化合物に繋がる。このことはまた、活性成分として本発明の化合物を有する薬学的組成物へと、そして哺乳動物における一連の状態(例えば、種々の起源および病因学の疼痛(例えば、急性疼痛、慢性疼痛、炎症性疼痛およびニューロパシー性疼痛)、歯痛および頭痛(例えば、偏頭痛、群発性頭痛、および緊張性頭痛)であるが、これらに限定されない)を処置、予防または緩和するための、それら化合物の使用に繋がる。
Aは、N、CR4、Lと結合した炭素原子であるか、または原子でなく;
Aが原子でない場合、W、Z、B、YおよびXのうちの1つがLと結合した炭素原子であり、W、Z、B、YおよびXのうちの別の1つがGと結合した炭素原子であり、そしてW、Z、B、YおよびXのうちの残りの各々が独立してNまたはCR4であり;
Lは置換または非置換の−(C−C)−、−(CR5=CR6)−または−(C≡C)−であり;
Gは、C=O、C=SまたはSO2であり;
R1は、置換もしくは非置換の脂肪族、置換もしくは非置換のアルキル、置換もしくは非置換のヘテロアルキル、置換もしくは非置換のアリール、置換もしくは非置換のヘテロアリール、置換もしくは非置換のアラルキル、または置換もしくは非置換のヘテロアラルキルであり;
R2は、水素であるか、または置換もしくは非置換のアルキルであり;
R3は、置換または非置換の脂肪族、置換もしくは非置換のアルキル、置換もしくは非置換のヘテロアルキル、置換もしくは非置換のアリール、置換もしくは非置換のヘテロアリール、置換もしくは非置換のアラルキルまたは置換もしくは非置換のヘテロアラルキルであり;
各々のR4は、独立して、水素、アルキル、置換もしくは非置換のアルキル、アシル、アシルアミノ、アルキルアミノ、アルキルチオ、アルコキシ、アルコキシカルボニル、アルキルアリールアミノ、アリールアルキルオキシ、アミノ、アリール、アリールアルキル、スルホキシド、スルホン、スルファニル、アミノスルホニル、アリールスルホニル、硫酸、硫酸エステル、ジヒドロキシホスホリル、アミノヒドロキシホスホリル、アジド、カルボキシ、カルバモイル、カルボキシル、シアノ、シクロヘテロアルキル、ジアルキルアミノ、ハロ、ヘテロアリールオキシ、ヘテロアリール、ヘテロアルキル、ヒドロキシ、ニトロ、またはチオであり;そして
R5およびR6の各々は、独立して、H、ハロであるかまたは、置換もしくは非置換の脂肪族、置換もしくは非置換のアルキル、置換もしくは非置換のヘテロアルキル、置換もしくは非置換のアリール、置換もしくは非置換のヘテロアリール、置換もしくは非置換のアラルキルもしくは置換もしくは非置換のヘテロアラルキルである。
ここで、L、W、X、Y、Z、R1は式IAに関して定義されたとおりであり、そしてR3は式IAの第一の代替実施形態において定義されたとおりである。この第二の代替実施形態の特定の実施形態において、R1は、置換されたアルキルまたは−(CR2 2)X−R4’であり得る。R1が−(CR2 2)X−R4’である場合、R2は水素またはアルキルであり;R4’はR4であり、そしてR4は式1に関して記載されるとおりであり、そしてnは1〜3の整数である。この同じ実施形態において、R4’は、t−ブチル、アリール、シクロアルキル、シクロへテロアルキルおよびヘテロアリールから選択され得;そして代替的に、R4’は、置換もしくは非置換のフェニル、または置換もしくは非置換のナフチルから選択され得;さらに代替的に、R4’は、シクロプロピル、シクロペンチル、またはシクロヘキシルからなる群より選択され得;なおさらに、R4’は、置換もしくは非置換のピロリジニル、置換もしくは非置換のピペリジニル、または置換もしくは非置換のモルホリニルから選択され得;なおさらに、R4’は、置換もしくは非置換のピリジニル、または置換もしくは非置換のピリミジニルから選択され得;そしてさらに、R4’は、置換もしくは非置換のフラニル、置換もしくは非置換のイミダゾリル、置換もしくは非置換のチオフェニル、置換もしくは非置換のピラゾリル、または置換もしくは非置換のチアゾリルから選択され得る。R4’はまた、置換または非置換のベンゾジオキサニル、置換もしくは非置換のベンゾピラニル、置換もしくは非置換のインドリル、置換もしくは非置換のインダゾリル、置換もしくは非置換のメチレンジオキシフェニル、置換もしくは非置換のキノリニル、置換もしくは非置換のイソキノリニル、置換もしくは非置換のテトラヒドロキノリニル、置換もしくは非置換のテトラヒドロイソキノリニル、置換もしくは非置換のジヒドロキノリニル、または置換もしくは非置換のジヒドロイソキノリニルから選択され得る。特定の実施形態において、R4’はt−Buである。この実施形態における全ての前述の変数に関して、xは1または2である。
(定義)
化合物、このような化合物を含む薬学的組成物、ならびにこのような化合物および組成物を使用する方法を記載する場合、以下の用語は、他に示されない限り、以下の意味を有する。以下に定義される任意の部分は、種々の置換基で置換され得ること、およびそれぞれの定義はそれらの範囲内でそのような置換された部分を含むことを意図されることが、理解されるべきである。非限定的な例によって、このような置換基は、例えば、ハロ(例えば、フルオロ、クロロ、ブロモ)、−CN、−CF3、−OH、−OCF3、C2−6アルケニル、C3−6アルキニル、C1〜6アルコキシ、アリールおよびジ−C1〜6アルキルアミノを含み得る。
−ハロ、
−NO2、−NH2、−NHR、−N(R)2、
−NRCOR,−NRSOR,−NRSO2R、OH、CN,CO2R、
−CO2H、
−R−OH、−O−R、−COOR、
−CON(R)2、−CONROR、
−SO2H、−R−S、−SO2N(R)2、
−S(O)R、−S(O)2R、ここで、各々のRは、独立して、アリールまたは脂肪族であり、必要に応じて置換基を有する。R基を含むヘテロ置換基のなかでも、本明細書中に定義されたアルキルのR基およびアリールのR基を有する物質が好ましい。本明細書中に好ましい置換基は、上記に列挙した置換基である。
本明細書中で先に記載されるように、本発明の化合物は、哺乳動物における広範な状態、とりわけ関節炎、パーキンソン病、アルツハイマー病、発作、ブドウ膜炎、喘息、心筋梗塞、疼痛症候群(急性および慢性、またはニューロパシー性)の処置および予防、外傷性脳損傷、急性脊髄損傷、神経変性障害、脱毛症(毛髪喪失)、炎症性腸疾患ならびに自己免疫障害または状態を、予防および/または処置するのに有用である。
薬剤として使用される場合、本発明のアミド化合物は、代表的に、薬学的組成物の形態で投与される。このような組成物は、当該薬学的分野において周知の様式で調製され得、そして少なくとも1つの活性な化合物を含み得る。
式Iの化合物を、乾燥ゼラチン結合剤と、約1:2の重量比で乾燥粉末として混合する。少量のステアリン酸マグネシウムを滑沢剤として添加する。この混合物を、錠剤プレスにおいて240〜270mgの錠剤(錠剤1つあたり80〜90mgの活性化合物)に形成する。
式Iの化合物を、デンプン希釈剤と、約1:1の重量比で乾燥粉末として混合する。この混合物を、250mgのカプセル(カプセル1つあたり125mgの活性化合物)中に充填する。
式Iの化合物(125mg)、ショ糖(1.75g)およびキサントガム(4mg)を混合し、10号メッシュU.S.篩を通し、次いで予め作製した、水中の微結晶セルロースとカルボキシメチルセルロースナトリウム(11:89、50mg)との溶液と混合する。安息香酸ナトリウム(10mg)(香味剤)および着色剤を水で希釈し、そして撹拌しながら添加する。次いで、十分な水を添加して、総量5mLを生成する。
式Iの化合物を、乾燥ゼラチン結合剤と、約1:2の重量比で乾燥粉末として混合する。少量のステアリン酸マグネシウムを滑沢剤として添加する。この混合物を、錠剤プレスにおいて450〜900mgの錠剤(錠剤1つあたり150〜300mgの活性化合物)に形成する。
式Iの化合物を緩衝化した注射可能な滅菌生理食塩水中に、約5mg/mlの濃度に溶解するかまたは懸濁する。
ステアリルアルコール(250g)および白色ワセリン(250g)を約75℃で溶解し、次いで、水(約370g)に溶解した式Iの化合物(50g)、メチルパラベン(0.25g)、プロピルパラベン(0.15g)、ラウリル硫酸ナトリウム(10g)、およびプロピレングリコール(120g)の混合物を添加し、そして得られた混合物を硬化するまで撹拌する。
本発明の化合物は、哺乳動物の状態の処置のための治療剤として使用される。従って、本発明の化合物または薬学的組成物は、人を含む哺乳動物における神経変性状態、自己免疫状態および炎症性状態を予防および/または処置するための治療剤としての用途を見出す。
本発明の化合物は、以下の一般的な方法および手順を使用して、容易に利用可能な出発物質から調製され得る。代表的または好ましい処理条件(すなわち、反応温度、反応時間、反応物のモル比、溶媒、圧力など)が与えられるが、他の処理条件もまた他に示されない限り使用され得ることが、理解される。最適な反応条件は、特定の反応物または使用される溶媒で変動し得るが、そのような条件は、慣用的な最適化手順によって当業者により決定され得る。
(中間体1)
(4−((E)−3,3−ジメチル−ブタ−1−エニル)−安息香酸)
(((E)−4−ペンタ−1−エニル)−安息香酸)
(6−(3,3−ジメチルブタ−1−イニル)ニコチン酸)
MS:MH+=204。
(4−(3,3−ジメチルブタ−1−イニル)安息香酸)
MS:MH+=203。
(2,2,2−トリフルオロエチルジフェニルホスフィンオキシド)
MS:MH+=286。
MS:MH+=217。
(実施例1)
(ベンズアミドの代表的な合成)
冷却し(0℃)、そしてよく撹拌した、EtOAcおよびDMFの混合物(1:1、25mL)中の4−(3,3−ジメチル−ブタ−1−エニル)−安息香酸(1.5g、7.34mMol)の懸濁液に、塩化オキサリル(0.364g、4.04mMol)を徐々に滴下し、そしてこの混合物を1時間撹拌した。次いで、EtOAc(5mL)中のm−アンシジン(Anisidine)(1.36g、11.01mMol)を添加し、そしてこの混合物を6.0時間撹拌し、その後、飽和炭酸カリウム溶液でクエンチした。沈殿物を濾過し、水で洗浄しそして減圧乾燥させて、表題の化合物を得た。
(自動化パラレル合成方法を使用したベンズアミド代表的な合成)
適切な安息香酸(2mmol)を15mlのクロロホルム中に溶解または懸濁し、そして20mmolの塩化チオニルで処理した。この反応混合物を15分間還流し、そして溶媒を減圧下で除去した。その残渣を、4mlの無水クロロホルムに溶解し、そしてこの溶液の60μl(30μmole)を96ウェルガラスプレートの各々のウェルに加えた。次いで、適切なアミン(60μmole)を対応するウェルに添加し、その後N,N−ジイソプロピルエチルアミン(120μmole)を添加した。次いで、このプレートを65℃で15分間加熱した。HT−12 Genevac遠心分離エバキュエーターを使用して溶媒を除去し、そして各々のウェルに100μlのDMSOを添加し、そして化合物を96ウェルポリプロピレン反応プレートに移した。次いでこのプレートをABgeneプレートシーラーを使用して密封し、そしてLC−MS精製に供した。
Shimadzu LCポンプを取り付けたPerkin Elmer API100質量分析計を使用して、これらのライブラリーを精製した。使用したクロマトグラフィーの方法は、1分当たり6mlの流速で、8分間にわたる10〜100%のアセトニトリル:水の勾配であった。使用したカラムは、10×50mm YMC C18であり、そして化合物をGilson 204フラクションコレクタを使用して収集した。
以下の化合物を本発明の方法に従って調製し、そして以下の表1に記載する。この表の目的のため、各々の化合物の生物学的活性を、以下の添え書きで注記したように表した。これは、この表の総括において参考にされるべきである:
「+」 カプサイシン刺激によって誘導されたカルシウムイオンの流入について、0〜25%の阻害を示した化合物
「++」 カプサイシン刺激によって誘導されたカルシウムイオンの流入について、25〜50%の阻害を示した化合物
「+++」 カプサイシン刺激によって誘導されたカルシウムイオンの流入について、50〜75%の阻害を示した化合物
「++++」 カプサイシン刺激によって誘導されたカルシウムイオンの流入について、75%以上の阻害を示した化合物
「++++」によって表わされる阻害百分率を有する化合物が、特に有益である。
(カルシウム画像化アッセイ)
VR1タンパク質は、熱ゲート操作性カチオンチャネルであり、これはナトリウムイオン毎につき約10個のカルシウムイオンを交換して、神経細胞膜の脱分極および細胞内カルシウム濃度の上昇を生じる。従って、VR1レセプターにおける化合物の機能活性は、ニューロン(例えば、脊髄神経節)における細胞内カルシウムレベルの変化を測定することによって決定され得る。
(カルシウム画像化アッセイを使用した、インビトロでの効率の決定のための、VR1アンタゴニストの高スループット分析)
流体工学制御および温度制御を取り付けたベンチトップ走査型蛍光光度計(Flex Station,Molecular Devices)を使用して、96ウェルの様式で、二波長比率測定(ratiometric)色素(Fura2)をカルシウムイオンの相対レベルについての指標として使用した。
(ホールセルパッチクランプ電気生理学)
脊髄神経節(DRG)ニューロンを、新生仔ラットまたは成体ラットのいずれかより回収し、そしてポリ−D−リジンコーティングしたガラスカバーストリップ上にプレートした。プレートされたニューロンをチャンバ内に移して、コンピューター制御電磁弁ベースの灌流系を使用して、薬物をこれら細胞に添加した。これらの細胞を、標準的なDICオプティックスを使用して画像化した。細く引き延ばした(finely−pulled)ガラス電極を使用して、細胞をパッチした。pCLAMP8ソフトウェアにより増幅制御されたAxon Instruments Multiclampを使用して、電圧クランプ電気生理学実験を実施した。
Claims (41)
- 以下の式:
W、X、YおよびZの各々が、NおよびCR4から独立して選択され;
Lは、置換もしくは非置換の−(CR5=CR6)−であり;
GはC=Oであり;
R1は、置換もしくは非置換のシクロアルキル、または置換もしくは非置換のヘテロアリールであり;
R2は、水素であり;
R3は、CF3、n−プロピルまたは以下の式:
ここでR2’の各々は、R2’のうちの少なくとも2つがアルキルであるという条件で、水素またはアルキルであり;そしてここでアルキルである2つのR2’は、一緒になって3〜8個の原子のシクロアルキル環またはシクロヘテロアルキル環を形成し得;
各々のR4は、独立して、水素、アルキル、置換もしくは非置換のアルキル、アシル、アシルアミノ、アルキルアミノ、アルキルチオ、アルコキシ、アルコキシカルボニル、アルキルアリールアミノ、アリールアルキルオキシ、アミノ、アリール、アリールアルキル、スルフィニル、スルホニル、スルファニル、アミノスルホニル、アリールスルホニル、スルホ、置換スルホ、ジヒドロキシホスホリル、アミノヒドロキシホスホリル、アジド、カルボキシ、カルバモイル、カルボキシル、シアノ、シクロヘテロアルキル、ジアルキルアミノ、ハロ、ヘテロアリールオキシ、ヘテロアリール、ヘテロアルキル、ヒドロキシル、ニトロ、またはチオールであり;そして
R5およびR6の各々は、独立して、H、ハロであるかまたは、置換もしくは非置換の脂肪族、置換もしくは非置換のアルキル、置換もしくは非置換のヘテロアルキル、置換もしくは非置換のアリール、置換もしくは非置換のヘテロアリール、置換もしくは非置換のアラルキルまたは置換もしくは非置換のヘテロアラルキルであり、
ここで、用語「置換」とは、1個以上の水素原子が各々独立して、同じ置換基(単数または複数)または別の置換基と置き換えられる基をいい、−X、−R 14 、−O − 、=O、−OR 14 、−SR 14 、−S − 、=S、−NR 14 R 15 、=NR 14 、−CX 3 、−CF 3 、−CN、−OCN、−SCN、−NO、−NO 2 、=N 2 、−N 3 ,−S(O) 2 O − 、−S(O) 2 OH,−S(O) 2 R 14 、−OS(O 2 )O − 、−OS(O) 2 R 14 、−P(O)(O − ) 2 、−P(O)(OR 14 )(O − )、−OP(O)(OR 14 )(OR 15 )、−C(O)R 14 、−C(S)R 14 、−C(O)OR 14 、−C(O)NR 14 R 15 、−C(O)O − 、−C(S)OR 14 、−NR 16 C(O)NR 14 R 15 、−NR 16 C(S)NR 14 R 15 、−NR 17 C(NR 16 )NR 14 R 15 および−C(NR 16 )NR 14 R 15 から選択される基であり、ここで、各々Xは独立してハロゲンであり;各々R 14 、R 15 、R 16 およびR 17 は、独立して、水素、アルキル、アリール、アリールアルキル、シクロアルキル、シクロヘテロアルキル、ヘテロアルキル、ヘテロアリール、ヘテロアリールアルキル、−NR 18 R 19 、−C(O)R 18 もしくは−S(O) 2 R 18 であるか、または必要に応じてR 18 とR 19 とはそれらの両方と結合する原子と一緒になって、シクロヘテロアルキル環を形成し;そしてR 18 およびR 19 は、独立して、水素、アルキル、アリール、アリールアルキル、シクロアルキル、シクロヘテロアルキル、ヘテロアルキル、ヘテロアリール、またはヘテロアリールアルキルである、
化合物。 - W、Z、XおよびYの各々がCHである、請求項1に記載の化合物。
- R1が、置換もしくは非置換のピリジニルまたは置換もしくは非置換のピリミジニルである、請求項1に記載の化合物。
- R1が、置換もしくは非置換のフラニル、置換もしくは非置換のイミダゾリル、置換もしくは非置換のチオフェニル、置換もしくは非置換のピラゾリルまたは置換もしくは非置換のチアゾリルである、請求項1に記載の化合物。
- R1が、置換もしくは非置換のベンゾジオキサニル、置換もしくは非置換のベンゾピラニル、置換もしくは非置換のインドリル、置換もしくは非置換のインダゾリル、置換もしくは非置換のメチレンジオキシフェニル、置換もしくは非置換のキノリニル、置換もしくは非置換のイソキノリニル、置換もしくは非置換のテトラヒドロキノリニル、置換もしくは非置換のテトラヒドロイソキノリニル、置換もしくは非置換のジヒドロキノリニルまたは置換もしくは非置換のジヒドロイソキノリニルである、請求項1に記載の化合物。
- R1が、置換もしくは非置換のキノリニルまたは置換もしくは非置換のイソキノリニルである、請求項1に記載の化合物。
- W、X、YおよびZの各々がCR4である、請求項1に記載の化合物。
- WがNであり、そしてX、YおよびZの各々がCR4である、請求項1に記載の化合物。
- YがNであり、そしてW、XおよびZの各々がCR4である、請求項1に記載の化合物。
- W、X、YおよびZのうちのいずれか2つがNである、請求項1に記載の化合物。
- R5およびR6のうちの一方がメチルであり、他方が水素である、請求項1に記載の化合物。
- R5およびR6の各々が水素である、請求項1に記載の化合物。
- R3が、t−Bu、i−Pr、シクロプロピルまたはシクロブチルである、請求項1に記載の化合物。
- R3がCF3である、請求項1に記載の化合物。
- 以下の式:
W、X、YおよびZの各々が、独立してCR4から選択され;
R1が、置換もしくは非置換のシクロアルキル、置換もしくは非置換のシクロヘテロアルキルまたは置換もしくは非置換のヘテロアリールであり;
各々のR4は、独立して、水素、アルキル、置換もしくは非置換のアルキル、アシル、アルキルチオ、アルコキシ、アルコキシカルボニル、アリールアルキルオキシ、アリール、アリールアルキル、スルフィニル、スルホニル、スルファニル、アミノスルホニル、アリールスルホニル、スルホ、置換スルホ、ジヒドロキシホスホリル、アミノヒドロキシホスホリル、アジド、カルボキシ、カルバモイル、カルボキシル、シアノ、シクロヘテロアルキル、ジアルキルアミノ、ハロ、ヘテロアリールオキシ、ヘテロアリール、ヘテロアルキル、ヒドロキシル、ニトロ、またはチオールである、化合物。 - W、X、YおよびZの各々がCHである、請求項15に記載の化合物。
- R1が、置換もしくは非置換のピロリル、置換もしくは非置換のピリジニル、置換もしくは非置換のピリミジニル、置換もしくは非置換のフラニル、置換もしくは非置換のイミダゾリル、置換もしくは非置換のチオフェニル、置換もしくは非置換のピラゾリルまたは置換もしくは非置換のチアゾリルである、請求項15または16に記載の化合物。
- R1が、置換もしくは非置換のベンゾジオキサニル、置換もしくは非置換のベンゾピラニル、置換もしくは非置換のインドリル、置換もしくは非置換のインダゾリル、置換もしくは非置換のメチレンジオキシフェニル、置換もしくは非置換のキノリニル、置換もしくは非置換のイソキノリニル、置換もしくは非置換のテトラヒドロキノリニル、置換もしくは非置換のテトラヒドロイソキノリニル、置換もしくは非置換のジヒドロキノリニルまたは置換もしくは非置換のジヒドロイソキノリニルである、請求項15または16に記載の化合物。
- 請求項1に記載の化合物、またはその薬学的に受容可能な塩もしくは立体異性体であって、該化合物が、以下:
- 請求項1に記載の化合物、またはその薬学的に受容可能な塩もしくは立体異性体であって、該化合物が、以下:
- 請求項1に記載の化合物、またはその薬学的に受容可能な塩もしくは立体異性体であって、該化合物が、以下:
- 請求項1に記載の化合物、またはその薬学的に受容可能な塩もしくは立体異性体であって、該化合物が、以下:
- 薬学的に受容可能なキャリアおよび薬学的に有効な量の請求項1に記載の化合物を含む、薬学的組成物。
- 前記キャリアが非経口用である、請求項23に記載の薬学的組成物。
- 前記キャリアが経口用である、請求項23に記載の薬学的組成物。
- 前記キャリアが局所用である、請求項23に記載の薬学的組成物。
- 疼痛状態、神経性疾患もしくは神経性状態、または神経変性疾患もしくは神経変性状態、自己免疫疾患、あるいは、炎症性の疾患もしくは状態を処置または予防するための医薬として使用するための、請求項23に記載の組成物。
- 前記医薬が、疼痛状態を処置または予防するためのものである、請求項23に記載の組成物。
- 前記医薬が、自己免疫疾患を処置または予防するためのものである、請求項23に記載の組成物。
- 前記医薬が、炎症性の疾患または状態を処置または予防するためのものである、請求項23に記載の組成物。
- 前記医薬が、神経性疾患もしくは神経性状態、または神経変性疾患もしくは神経変性状態を処置または予防するためのものである、請求項23に記載の組成物。
- 疼痛、急性疼痛、炎症性疼痛、ニューロパシー性疼痛、慢性疼痛、歯痛;頭痛、偏頭痛、群発性頭痛、緊張性頭痛;パーキンソン病;アルツハイマー病;多発性硬化症;神経性炎症、外傷性脳損傷、発作または脳炎により媒介されるかまたは神経性炎症、外傷性脳損傷、発作または脳炎を生じる疾患または障害;中心性に媒介される神経性精神医学的疾患または障害、鬱病、躁病、双極性疾患、不安、統合失調症、摂食障害、睡眠障害、認識障害、癲癇障害、痙攣障害;前立腺不全、膀胱不全、腸不全、尿失禁、排尿躊躇、直腸過敏症、便失禁、良性前立腺肥大、炎症性腸疾患;呼吸性または気道性の疾患または障害、アレルギー性鼻炎、喘息、反応性気道疾患、慢性閉塞性肺疾患;炎症により媒介されるかまたは炎症を生じる疾患または障害、関節炎、慢性関節リウマチ、変形性関節症;心筋梗塞;自己免疫疾患または自己免疫障害;ブドウ膜炎、アテローム性硬化症;痒み、掻痒、乾癬;脱毛症;肥満;脂質障害;癌;高血圧;脊髄損傷;あるいは腎臓障害を処置または防止するための医薬として使用するための、請求項23に記載の組成物。
- 前記医薬がパーキンソン病を処置または予防するためのものである、請求項27に記載の組成物。
- 前記医薬がアルツハイマー病を処置または予防するためのものである、請求項27に記載の組成物。
- 前記医薬が外傷性脳損傷を処置または予防するためのものである、請求項27に記載の組成物。
- 前記医薬が発作を処置または予防するためのものである、請求項27に記載の組成物。
- 前記医薬が疼痛を処置または予防するためのものである、請求項27に記載の組成物。
- 前記医薬がニューロパシー性疼痛を処置または予防するためのものである、請求項27に記載の組成物。
- カプサイシンへの曝露の症状、熱への曝露に起因する火傷または刺激の症状、光への曝露に起因する火傷または刺激の症状、火傷の症状、催涙ガスへの曝露に起因する気管支収縮または刺激、あるいは酸への曝露に起因する火傷または曝露刺激の症状を処置するための医薬として使用するための、請求項27に記載の組成物。
- 前記医薬が、***切除術後の疼痛症候群、断端疼痛、幻想肢痛、咽頭ニューロパシー性疼痛、シャルコー疼痛、歯痛、毒蛇の咬傷、蜘蛛の咬傷、虫刺され、疱疹後の神経痛、糖尿病性ニューロパシー、反射***感神経性ジストロフィ、三叉神経痛、変形性関節症、慢性関節リウマチ、線維筋痛症、ギヤン−バレー症候群、感覚異常性大腿神経痛、口内焼灼感症候群、両側性末梢ニューロパシー、カウザルギー、坐骨神経炎、末梢神経炎、多発性神経炎、分節性神経炎、ゴンボー神経炎、ニューロン炎、頚腕神経痛、頭側神経痛、膝神経痛、舌咽頭筋神経痛、偏頭痛性神経痛、特発性神経痛、肋間神経痛、***神経痛、顎関節神経痛、モートン神経痛、鼻毛様体神経痛、後頭神経痛、紅色神経痛、スラダー神経痛、脾臓口蓋神経痛、眼窩上神経痛、ヴィディウス神経痛、洞頭痛、緊張頭痛、分娩、出産、腸管ガス、月経、癌または外傷を処置または予防するためのものである、請求項27に記載の組成物。
- 請求項1に記載の化合物の調製方法であって、該方法は、以下の式:
W、X、YおよびZの各々が、NおよびCR4から独立して選択され;
Lは、置換もしくは非置換の−(CR5=CR6)−であり;
R1は、置換もしくは非置換のシクロアルキル、または置換もしくは非置換のヘテロアリールであり;
R2は、水素であり;
R3は、CF3、n−プロピルまたは以下の式:
ここでR2’の各々は、R2’のうちの少なくとも2つがアルキルであるという条件で、水素またはアルキルであり;そしてここでアルキルである2つのR2’は、一緒になって3〜8個の原子のシクロアルキル環またはシクロヘテロアルキル環を形成し得;
各々のR4は、独立して、水素、アルキル、置換もしくは非置換のアルキル、アシル、アシルアミノ、アルキルアミノ、アルキルチオ、アルコキシ、アルコキシカルボニル、アルキルアリールアミノ、アリールアルキルオキシ、アミノ、アリール、アリールアルキル、スルフィニル、スルホニル、スルファニル、アミノスルホニル、アリールスルホニル、スルホ、置換スルホ、ジヒドロキシホスホリル、アミノヒドロキシホスホリル、アジド、カルボキシ、カルバモイル、カルボキシル、シアノ、シクロヘテロアルキル、ジアルキルアミノ、ハロ、ヘテロアリールオキシ、ヘテロアリール、ヘテロアルキル、ヒドロキシル、ニトロ、またはチオールであり;そして
R5およびR6の各々は、独立して、H、ハロであるかまたは、置換もしくは非置換の脂肪族、置換もしくは非置換のアルキル、置換もしくは非置換のヘテロアルキル、置換もしくは非置換のアリール、置換もしくは非置換のヘテロアリール、置換もしくは非置換のアラルキルまたは置換もしくは非置換のヘテロアラルキルである、方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US50888403P | 2003-10-07 | 2003-10-07 | |
PCT/US2004/033163 WO2005046683A1 (en) | 2003-10-07 | 2004-10-07 | Amide derivatives as ion-channel ligands and pharmaceutical compositions and methods of using the same |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2007509043A JP2007509043A (ja) | 2007-04-12 |
JP2007509043A5 JP2007509043A5 (ja) | 2008-07-31 |
JP4667384B2 true JP4667384B2 (ja) | 2011-04-13 |
Family
ID=34590097
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2006534356A Expired - Fee Related JP4667384B2 (ja) | 2003-10-07 | 2004-10-07 | イオンチャネルリガンドとしてのアミド誘導体および薬学的組成物、ならびにこれらを使用する方法 |
Country Status (9)
Country | Link |
---|---|
US (2) | US7432281B2 (ja) |
EP (1) | EP1680109A4 (ja) |
JP (1) | JP4667384B2 (ja) |
AR (1) | AR046276A1 (ja) |
BR (1) | BRPI0415179A (ja) |
CA (1) | CA2541949A1 (ja) |
MX (1) | MXPA06003951A (ja) |
TW (1) | TW200526631A (ja) |
WO (1) | WO2005046683A1 (ja) |
Families Citing this family (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4667384B2 (ja) * | 2003-10-07 | 2011-04-13 | レノビス, インコーポレイテッド | イオンチャネルリガンドとしてのアミド誘導体および薬学的組成物、ならびにこれらを使用する方法 |
AP2007004119A0 (en) * | 2005-02-28 | 2007-08-31 | Renovis Inc | Amide derivatives as ion-channel ligands and pharmaceutical compositions and methods of using the same |
US7576099B2 (en) | 2005-02-28 | 2009-08-18 | Renovis, Inc. | Amide derivatives as ion-channel ligands and pharmaceutical compositions and methods of using the same |
US20080300243A1 (en) * | 2005-02-28 | 2008-12-04 | Kelly Michael G | Amide Derivatives as Ion-Channel Ligands and Pharmaceutical Compositions and Methods of Using the Same |
US7312233B2 (en) * | 2005-03-14 | 2007-12-25 | Renovis, Inc. | Amide derivatives as ion-channel ligands and pharmaceutical compositions and methods of using the same |
CA2616079C (en) | 2005-07-22 | 2012-09-25 | Mochida Pharmaceutical Co., Ltd. | Novel heterocyclidene acetamide derivative |
EP1764096A1 (en) | 2005-09-20 | 2007-03-21 | Revotar Biopharmaceuticals AG | Novel phloroglucinol derivatives having selectin ligand activity |
EP1764093A1 (en) | 2005-09-20 | 2007-03-21 | Revotar Biopharmaceuticals AG | Novel aromatic compounds and their use in medical applications |
CA2641781A1 (en) * | 2006-02-23 | 2007-09-07 | Renovis, Inc. | Amide derivatives as ion-channel ligands and pharmaceutical compositions and methods of using the same |
JP5255559B2 (ja) | 2006-03-31 | 2013-08-07 | アボット・ラボラトリーズ | インダゾール化合物 |
PE20081692A1 (es) | 2007-01-24 | 2008-12-18 | Mochida Pharm Co Ltd | Nuevo derivado de heterocicliden acetamida |
WO2008096755A1 (ja) * | 2007-02-07 | 2008-08-14 | Nippon Suisan Kaisha, Ltd. | バニロイド受容体(vr1)阻害剤及びその用途 |
DK2124562T3 (en) * | 2007-03-09 | 2016-08-01 | Second Genome Inc | BICYCLOHETEROARYLFORBINDELSER AS P2X7 modulators and uses thereof |
US8853392B2 (en) | 2007-06-03 | 2014-10-07 | Vanderbilt University | Benzamide mGluR5 positive allosteric modulators and methods of making and using same |
MX2009013169A (es) * | 2007-06-03 | 2010-04-30 | Univ Vanderbilt | Moduladores alostericos positivos del mglur5 benzamida y metodos de elaboracion y uso de los mismos. |
JP2009108036A (ja) * | 2007-09-28 | 2009-05-21 | Fujifilm Corp | 新規アセチレン化合物、その製造方法、それを構成単位として含むポリマー、該化合物及び/又は該ポリマーを含む組成物、該組成物を硬化させてなる硬化物 |
CN101906056B (zh) * | 2009-06-04 | 2013-10-30 | 中国科学院广州生物医药与健康研究院 | 作为m2抑制剂的环烷胺类化合物及其应用 |
US9452980B2 (en) * | 2009-12-22 | 2016-09-27 | Hoffmann-La Roche Inc. | Substituted benzamides |
US8710043B2 (en) | 2011-06-24 | 2014-04-29 | Amgen Inc. | TRPM8 antagonists and their use in treatments |
WO2013078413A1 (en) * | 2011-11-22 | 2013-05-30 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Modulators of lipid storage |
US8952009B2 (en) | 2012-08-06 | 2015-02-10 | Amgen Inc. | Chroman derivatives as TRPM8 inhibitors |
ES2819830T3 (es) | 2016-03-17 | 2021-04-19 | Hoffmann La Roche | Derivado de 5-etiol-4-metil-pirazol-3-carboxamida que tiene actividad como agonista de TAAR |
CN108503899B (zh) * | 2018-05-28 | 2020-05-22 | 深圳先进技术研究院 | ***仿体及其制备方法与应用 |
AU2019318046A1 (en) * | 2018-08-06 | 2021-01-14 | Dana-Farber Cancer Institute, Inc. | Histone demethylase 5 inhibitors and uses thereof |
US11643394B2 (en) | 2020-04-30 | 2023-05-09 | Icahn School Of Medicine At Mount Sinai | Krüppel-like factor 15 (KLF15) small molecule agonists in kidney disease |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5612352A (en) * | 1979-07-11 | 1981-02-06 | Asahi Chem Ind Co Ltd | Ai-77, medically permissible salt thereof and their preparation |
WO2001023383A1 (fr) * | 1999-09-28 | 2001-04-05 | Eisai Co., Ltd. | Composes de quinuclidine et medicaments contenant ces composes comme principe actif |
JP2002528537A (ja) * | 1998-10-30 | 2002-09-03 | フアルマシア・エ・アツプジヨン・エツセ・ピー・アー | 2−アミノ−チアゾール誘導体類、それらの製造方法および抗癌剤としてのそれらの使用 |
JP2003503350A (ja) * | 1999-06-30 | 2003-01-28 | 第一製薬株式会社 | Vla−4インヒビター化合物 |
Family Cites Families (86)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3346584A (en) * | 1964-09-23 | 1967-10-10 | Union Carbide Corp | 2-polychloroalkylbenzothiazolines |
US3424760A (en) * | 1966-03-07 | 1969-01-28 | Robins Co Inc A H | 3-ureidopyrrolidines |
US3424761A (en) * | 1966-03-07 | 1969-01-28 | Robins Co Inc A H | 3-ureidopyrrolidines |
NO133758C (ja) * | 1970-04-04 | 1976-06-23 | Takeda Chemical Industries Ltd | |
GB2058047B (en) | 1979-07-11 | 1983-09-21 | Asahi Chemical Ind | Amides and amidines |
JPS58105229A (ja) * | 1981-12-18 | 1983-06-23 | Fuji Photo Film Co Ltd | カラ−写真感光材料 |
US4760161A (en) | 1983-04-25 | 1988-07-26 | Merck & Co., Inc. | Ipoxygenase inhibitors |
US4579866A (en) * | 1984-05-29 | 1986-04-01 | Usv Pharmaceutical Corp. | Phenylacetamides as anti-allergy, anti-asthma and anti-inflammatory agents |
FR2567887B1 (fr) | 1984-07-19 | 1986-12-19 | Rhone Poulenc Sante | Nouveaux amides substitues, leur preparation et les medicaments qui les contiennent |
GB9125924D0 (en) | 1991-06-18 | 1992-02-05 | Orion Yhtymae Oy | Stereoisomers of an imidazole derivative |
DE59304166D1 (de) | 1992-07-01 | 1996-11-21 | Hoechst Ag | 3,4,5-Substituierte Benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
JPH11503435A (ja) | 1995-04-08 | 1999-03-26 | ビーエーエスエフ アクチェンゲゼルシャフト | 有害菌類を抑制する方法 |
IT1277597B1 (it) | 1995-09-15 | 1997-11-11 | Smithkline Beecham Spa | Derivati di diarilalchenilammina |
EP0876345B1 (en) | 1995-10-16 | 2004-08-18 | Fujisawa Pharmaceutical Co., Ltd. | Heterocyclic compounds as h+-atpases |
US6221865B1 (en) | 1995-11-06 | 2001-04-24 | University Of Pittsburgh | Inhibitors of protein isoprenyl transferases |
JP3285746B2 (ja) * | 1995-11-24 | 2002-05-27 | 株式会社資生堂 | フェニレンジアミン誘導体及びラジカルスカベンジャー、脳梗塞抑制剤、脳浮腫抑制剤 |
KR19990082330A (ko) | 1996-02-06 | 1999-11-25 | 미즈노 마사루 | 신규 화합물 및 이의 의약 용도 |
EP0915086A4 (en) | 1996-05-24 | 2001-01-17 | Ono Pharmaceutical Co | PHENYLSULFONAMIDE DERIVATIVES |
IL127559A0 (en) | 1996-06-20 | 1999-10-28 | Univ Texas | Compounds and methods for providing pharmacologically active preparations and uses thereof |
WO1998032741A1 (en) | 1997-01-29 | 1998-07-30 | Zeneca Limited | Inhibitors of farnesyl protein transferase |
AU7371998A (en) | 1997-05-07 | 1998-11-27 | University Of Pittsburgh | Inhibitors of protein isoprenyl transferases |
TW544448B (en) * | 1997-07-11 | 2003-08-01 | Novartis Ag | Pyridine derivatives |
US6555584B1 (en) * | 2000-06-29 | 2003-04-29 | Ajinomoto Co., Inc. | Acylsulfonamide derivative |
JPH11171848A (ja) * | 1997-09-26 | 1999-06-29 | Fujirebio Inc | 芳香族アミド誘導体 |
ES2221996T3 (es) * | 1997-10-07 | 2005-01-16 | Ortho-Mcneil Pharmaceutical, Inc. | Derivados de dipirido-imidazol utiles para el tratamiento de trastornos del sistema nervioso central. |
JP3337992B2 (ja) * | 1997-11-04 | 2002-10-28 | ファイザー製薬株式会社 | 5−置換ピコリン酸化合物及びその製造方法 |
AU2435199A (en) | 1998-02-10 | 1999-08-30 | Astrazeneca Uk Limited | Farnesyl transferase inhibitors |
CA2325638A1 (en) | 1998-03-26 | 1999-09-30 | Hideki Yamada | Amide derivatives and nociceptin antagonists |
WO1999062885A1 (en) * | 1998-06-05 | 1999-12-09 | Boehringer Ingelheim Pharmaceuticals, Inc. | Substituted 1-(4-aminophenyl)pyrazoles and their use as anti-inflammatory agents |
WO2000015213A1 (fr) | 1998-09-11 | 2000-03-23 | Shionogi & Co., Ltd. | Agent de prevention ou de traitement de l'insuffisance cardiaque congestive |
US6331640B1 (en) | 1998-10-13 | 2001-12-18 | Hoffmann-La Roche Inc. | Diaminopropionic acid derivatives |
JP2002533476A (ja) | 1998-12-23 | 2002-10-08 | アストラゼネカ アクチボラグ | 化学化合物 |
US6316503B1 (en) | 1999-03-15 | 2001-11-13 | Tularik Inc. | LXR modulators |
NZ527771A (en) | 1999-08-04 | 2005-04-29 | Icagen Inc | Methods for treating or preventing anxiety |
EP1208085B1 (en) | 1999-08-04 | 2007-12-05 | Icagen, Inc. | Benzanilides as potassium channel openers |
WO2001021615A1 (en) * | 1999-09-17 | 2001-03-29 | Yamanouchi Pharmaceutical Co., Ltd. | Benzimidazole derivatives |
MX228790B (es) | 1999-09-17 | 2005-06-30 | Millennium Pharm Inc | Inhibidores del factor xa. |
US6632815B2 (en) * | 1999-09-17 | 2003-10-14 | Millennium Pharmaceuticals, Inc. | Inhibitors of factor Xa |
WO2001021160A2 (en) | 1999-09-23 | 2001-03-29 | Axxima Pharmaceuticals Aktiengesellschaft | Carboxymide and aniline derivatives as selective inhibitors of pathogens |
JP5278983B2 (ja) | 1999-11-17 | 2013-09-04 | 塩野義製薬株式会社 | アミド化合物の新規用途 |
JP2003519676A (ja) | 2000-01-13 | 2003-06-24 | トゥラリック インコーポレイテッド | 抗菌剤 |
EP1257536A1 (en) | 2000-01-27 | 2002-11-20 | Cytovia, Inc. | Substituted nicotinamides and analogs as activators of caspases and inducers of apoptosis and the use thereof |
WO2001064642A2 (en) | 2000-02-29 | 2001-09-07 | Cor Therapeutics, Inc. | Benzamides and related inhibitors of factor xa |
WO2001082916A2 (en) | 2000-05-03 | 2001-11-08 | Tularik Inc. | Combination therapeutic compositions and methods of use |
JP2002055409A (ja) | 2000-08-08 | 2002-02-20 | Fuji Photo Film Co Ltd | 熱現像感光材料 |
CA2430409A1 (en) | 2000-11-28 | 2002-06-06 | Guilford Pharmaceuticals Inc. | Bisubstituted carbocyclic cyclophilin binding compounds and their use |
KR20030064852A (ko) | 2000-12-22 | 2003-08-02 | 이시하라 산교 가부시끼가이샤 | 아닐린 유도체 또는 그의 염 및 이들을 함유하는사이토카인 생산 억제제 |
WO2002053101A2 (en) | 2000-12-29 | 2002-07-11 | Alteon, Inc. | Method for treating fibrotic diseases or other indications |
CA2435829A1 (en) * | 2001-01-25 | 2002-08-01 | Guilford Pharmaceuticals Inc. | Trisubstituted carbocyclic cyclophilin binding compounds and their use |
DOP2002000333A (es) | 2001-02-14 | 2002-09-30 | Warner Lambert Co | Derivados de acido isoftalico como inhibidores de metaloproteinasas de la matriz |
DOP2002000332A (es) | 2001-02-14 | 2002-08-30 | Warner Lambert Co | Inhibidores de piridina de metaloproteinasas de la matriz |
UA76977C2 (en) | 2001-03-02 | 2006-10-16 | Icos Corp | Aryl- and heteroaryl substituted chk1 inhibitors and their use as radiosensitizers and chemosensitizers |
WO2002094766A1 (fr) | 2001-05-18 | 2002-11-28 | Nihon Nohyaku Co., Ltd. | Derive de phtalamide, insecticide agricole et horticole et son utilisation |
DE10154689A1 (de) | 2001-11-09 | 2003-05-22 | Probiodrug Ag | Substituierte Aminoketonverbindungen |
US7491748B2 (en) | 2001-08-09 | 2009-02-17 | Ono Pharmaceutical Co., Ltd. | Carboxylic acid derivative compounds and drugs comprising these compounds as the active ingredient |
US20030130343A1 (en) | 2001-08-10 | 2003-07-10 | Adipogenix, Inc. | Fat accumulation-modulating compounds |
SE0102764D0 (sv) | 2001-08-17 | 2001-08-17 | Astrazeneca Ab | Compounds |
AUPR738301A0 (en) | 2001-08-30 | 2001-09-20 | Starpharma Limited | Chemotherapeutic agents |
BR0212510A (pt) | 2001-09-14 | 2004-08-24 | Methylgene Inc | Inibidor de histona desacetilase, composto e composição |
US6897220B2 (en) * | 2001-09-14 | 2005-05-24 | Methylgene, Inc. | Inhibitors of histone deacetylase |
US7429593B2 (en) * | 2001-09-14 | 2008-09-30 | Shionogi & Co., Ltd. | Utilities of amide compounds |
US20030187026A1 (en) * | 2001-12-13 | 2003-10-02 | Qun Li | Kinase inhibitors |
US20040157919A1 (en) * | 2002-01-25 | 2004-08-12 | Yong-Qian Wu | Trisubstituted carbocyclic cyclophilin binding compounds and their use |
AR038420A1 (es) | 2002-02-15 | 2005-01-12 | Glaxo Group Ltd | Compuesto de amida, procedimiento para la preparacion del mismo, su uso para la fabricacion de un medicamento y composicion farmaceutica que lo comprende |
KR101116627B1 (ko) | 2002-06-27 | 2012-10-09 | 노보 노르디스크 에이/에스 | 치료제로서 아릴 카르보닐 유도체 |
WO2004009549A2 (en) | 2002-07-18 | 2004-01-29 | Actelion Pharmaceuticals Ltd | Piperidines useful for the treatment of central nervous system disorders |
US20040110802A1 (en) | 2002-08-23 | 2004-06-10 | Atli Thorarensen | Antibacterial benzoic acid derivatives |
DE10238865A1 (de) * | 2002-08-24 | 2004-03-11 | Boehringer Ingelheim International Gmbh | Neue Carbonsäureamid-Verbindungen mit MCH-antagonistischer Wirkung, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
WO2004022536A1 (en) | 2002-09-04 | 2004-03-18 | Glenmark Pharmaceuticals Limited | New heterocyclic amide compounds useful for the treatment of inflammatory and allergic disorders: process for their preparation and pharmaceutical compositions containing them |
CA2501265A1 (en) | 2002-10-17 | 2004-04-29 | Methylgene Inc. | Inhibitors of histone deacetylase |
DK1585739T3 (da) | 2003-01-06 | 2011-06-20 | Lilly Co Eli | Substituerede arylcyclopropylacetamider som glucokinaseaktivatorer |
ES2552247T3 (es) | 2003-01-08 | 2015-11-26 | The University Of Washington | Agentes antibacterianos |
CA2514940A1 (en) | 2003-02-03 | 2004-08-19 | Janssen Pharmaceutica N.V. | Quinoline-derived amide modulators of vanilloid vr1 receptor |
BRPI0408136A (pt) | 2003-03-07 | 2006-03-01 | Astellas Pharma Inc | derivados heterocìclicos contendo nitrogênio tendo estirila 2,6-dissubstituìda |
AR045979A1 (es) | 2003-04-28 | 2005-11-23 | Astrazeneca Ab | Amidas heterociclicas |
CN100418948C (zh) | 2003-07-15 | 2008-09-17 | 麦克公司 | 羟基吡啶cgrp受体抗拮抗剂 |
AU2004264354A1 (en) | 2003-08-12 | 2005-02-24 | Amgen Inc. | Arylsulfonamidobenzylic compounds |
WO2005019176A1 (en) | 2003-08-25 | 2005-03-03 | Actelion Pharmaceuticals Ltd | Substituted amino-aza-cyclohexanes |
EP1669348A4 (en) * | 2003-09-30 | 2009-03-11 | Eisai R&D Man Co Ltd | NEW ANTIPILIC AGENT CONTAINING A HETEROCYCLIC COMPOUND |
JP4667384B2 (ja) | 2003-10-07 | 2011-04-13 | レノビス, インコーポレイテッド | イオンチャネルリガンドとしてのアミド誘導体および薬学的組成物、ならびにこれらを使用する方法 |
AU2005209257A1 (en) * | 2004-01-23 | 2005-08-11 | Amgen Inc. | Vanilloid receptor ligands and their use in treatments |
JP2005314347A (ja) | 2004-04-30 | 2005-11-10 | Japan Tobacco Inc | 疼痛抑制剤 |
TW200602314A (en) | 2004-05-28 | 2006-01-16 | Tanabe Seiyaku Co | A novel pyrrolidine compound and a process for preparing the same |
EP1775283A4 (en) * | 2004-07-14 | 2008-12-10 | Japan Tobacco Inc | 3-AMINOBENZAMIDE COMPOUND AND INHIBITORS OF THE ACTIVITY OF VANILLOID RECEPTOR 1 (VR1) |
US7576099B2 (en) | 2005-02-28 | 2009-08-18 | Renovis, Inc. | Amide derivatives as ion-channel ligands and pharmaceutical compositions and methods of using the same |
US20080300243A1 (en) * | 2005-02-28 | 2008-12-04 | Kelly Michael G | Amide Derivatives as Ion-Channel Ligands and Pharmaceutical Compositions and Methods of Using the Same |
-
2004
- 2004-10-07 JP JP2006534356A patent/JP4667384B2/ja not_active Expired - Fee Related
- 2004-10-07 BR BRPI0415179-8A patent/BRPI0415179A/pt not_active IP Right Cessation
- 2004-10-07 CA CA002541949A patent/CA2541949A1/en not_active Abandoned
- 2004-10-07 MX MXPA06003951A patent/MXPA06003951A/es not_active Application Discontinuation
- 2004-10-07 AR ARP040103646A patent/AR046276A1/es unknown
- 2004-10-07 WO PCT/US2004/033163 patent/WO2005046683A1/en active Application Filing
- 2004-10-07 US US10/961,483 patent/US7432281B2/en not_active Expired - Fee Related
- 2004-10-07 EP EP04794499A patent/EP1680109A4/en not_active Withdrawn
- 2004-10-07 TW TW093130317A patent/TW200526631A/zh unknown
-
2008
- 2008-07-18 US US12/218,973 patent/US20080312237A1/en not_active Abandoned
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5612352A (en) * | 1979-07-11 | 1981-02-06 | Asahi Chem Ind Co Ltd | Ai-77, medically permissible salt thereof and their preparation |
JP2002528537A (ja) * | 1998-10-30 | 2002-09-03 | フアルマシア・エ・アツプジヨン・エツセ・ピー・アー | 2−アミノ−チアゾール誘導体類、それらの製造方法および抗癌剤としてのそれらの使用 |
JP2003503350A (ja) * | 1999-06-30 | 2003-01-28 | 第一製薬株式会社 | Vla−4インヒビター化合物 |
WO2001023383A1 (fr) * | 1999-09-28 | 2001-04-05 | Eisai Co., Ltd. | Composes de quinuclidine et medicaments contenant ces composes comme principe actif |
Also Published As
Publication number | Publication date |
---|---|
MXPA06003951A (es) | 2006-06-27 |
WO2005046683A1 (en) | 2005-05-26 |
BRPI0415179A (pt) | 2006-11-28 |
CA2541949A1 (en) | 2005-05-26 |
EP1680109A1 (en) | 2006-07-19 |
JP2007509043A (ja) | 2007-04-12 |
AR046276A1 (es) | 2005-11-30 |
EP1680109A4 (en) | 2009-05-06 |
US20050222200A1 (en) | 2005-10-06 |
US20080312237A1 (en) | 2008-12-18 |
TW200526631A (en) | 2005-08-16 |
US7432281B2 (en) | 2008-10-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP4667384B2 (ja) | イオンチャネルリガンドとしてのアミド誘導体および薬学的組成物、ならびにこれらを使用する方法 | |
JP5608655B2 (ja) | P2x3受容体活性のモジュレーター | |
US8946439B2 (en) | Amide compounds, compositions and uses thereof | |
JP2007525482A (ja) | イオンチャネルリガンドとしてのアミド化合物およびその使用 | |
AU2004293416B2 (en) | Benzylether and benzylamino beta-secretase inhibitors for the treatment of Alzheimer's disease | |
CA3133753A1 (en) | Novel small molecule inhibitors of tead transcription factors | |
JP2007509846A (ja) | テトラヒドロ−ナフタレンおよび尿素誘導体 | |
JP6043298B2 (ja) | Trpm8受容体アンタゴニスト | |
CA3095451A1 (en) | Ox2r compounds | |
CN117440955A (zh) | 具有食欲素-2受体激动剂活性的取代的酰胺大环化合物 | |
GB2413129A (en) | Aromatic amide compounds as ion channel ligands and uses thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20071005 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20071005 |
|
A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080616 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20100721 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100727 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20101025 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20101101 |
|
A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20101126 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20101217 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20110111 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20140121 Year of fee payment: 3 |
|
R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
LAPS | Cancellation because of no payment of annual fees |