[go: up one dir, main page]

RU2014113973A - Фармацевтические соединения - Google Patents

Фармацевтические соединения Download PDF

Info

Publication number
RU2014113973A
RU2014113973A RU2014113973/04A RU2014113973A RU2014113973A RU 2014113973 A RU2014113973 A RU 2014113973A RU 2014113973/04 A RU2014113973/04 A RU 2014113973/04A RU 2014113973 A RU2014113973 A RU 2014113973A RU 2014113973 A RU2014113973 A RU 2014113973A
Authority
RU
Russia
Prior art keywords
group
compound
alkyl
formula
amino
Prior art date
Application number
RU2014113973/04A
Other languages
English (en)
Inventor
Эндрю Джеймс ВУДХЕД
Кристофер Чарльз Фредерик Гамлетт ГАМЛЕТТ
Гилберт Ибэй БЕСОНГ
Джанни ЧЕССАРИ
Мария Грация КАРР
Алессия МИЛЛЕМАДЖИ
Дэвид Нортон
Сьюзан Мария СААЛАУ-БЕТЕЛЛ
Хендрика Мария Герарда УИЛЛЕМС
Нейл Томас ТОМПСОН
Стивен Дуглас Хискок
Original Assignee
Астекс Терапьютикс Лимитед
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GBGB1118875.2A external-priority patent/GB201118875D0/en
Priority claimed from GB201118874A external-priority patent/GB201118874D0/en
Application filed by Астекс Терапьютикс Лимитед filed Critical Астекс Терапьютикс Лимитед
Publication of RU2014113973A publication Critical patent/RU2014113973A/ru

Links

Classifications

    • 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
    • C07D213/73—Unsubstituted amino or imino radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/275—Nitriles; Isonitriles
    • A61K31/277—Nitriles; Isonitriles having a ring, e.g. verapamil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4965—Non-condensed pyrazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C221/00—Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C225/00—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones
    • C07C225/02—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C225/14—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being unsaturated
    • C07C225/16—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C225/00—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones
    • C07C225/02—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C225/14—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being unsaturated
    • C07C225/16—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings
    • C07C225/18—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings the carbon skeleton containing also rings other than six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C225/00—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones
    • C07C225/22—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/38—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to acyclic carbon atoms and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C237/06—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C237/10—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms not being part of nitro or nitroso groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/24—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
    • C07C237/30—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to hydrogen atoms or to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C313/00—Sulfinic acids; Sulfenic acids; Halides, esters or anhydrides thereof; Amides of sulfinic or sulfenic acids, i.e. compounds having singly-bound oxygen atoms of sulfinic or sulfenic groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C313/02—Sulfinic acids; Derivatives thereof
    • C07C313/06—Sulfinamides
    • 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
    • C07D213/46—Oxygen atoms
    • C07D213/50—Ketonic radicals
    • 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
    • C07D213/63—One oxygen atom
    • C07D213/64—One oxygen atom attached in position 2 or 6
    • 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
    • C07D213/63—One oxygen atom
    • C07D213/65—One oxygen atom attached in position 3 or 5
    • 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
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • 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
    • C07D213/79—Acids; Esters
    • 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
    • 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
    • C07D213/84—Nitriles
    • 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
    • C07D213/89—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 with hetero atoms directly attached to the ring nitrogen atom
    • 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
    • C07D231/12—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • 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
    • C07D239/26—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • 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
    • C07D239/38—One sulfur atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having 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
    • C07D241/20—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
    • C07D275/02—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D277/28—Radicals substituted by nitrogen 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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/05—Isotopically modified compounds, e.g. labelled
    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Dermatology (AREA)
  • Biophysics (AREA)
  • Virology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Oncology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Communicable Diseases (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Pyridine Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Peptides Or Proteins (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

1. Соединение формулы (1):или соль, N-оксид, таутомер или стереоизомер указанного соединения, где:А представляет собой СН или азот;Е представляет собой СН или азот;Rвыбран из следующего:- ациклическая Cуглеводородная группа, возможно содержащая один или два заместителя R, причем один атом углерода в ациклической Cуглеводородной группе может быть необязательно заменен гетероатомом или группой, выбранными из О, S, NR, S(O) и SO, или два соседних атома углерода в ациклической d.углеводородной группе могут быть необязательно заменены группой, выбранной из CONR, NRCO, NRSOи SONR, при условии, что в каждом случае в ациклической Cуглеводородной группе сохраняется по меньшей мере один атом углерода; и- моноциклическая карбоциклическая или гетероциклическая группа, содержащая от 3 до 7 членов кольца, из которых 0, 1, 2, 3 или 4 членов кольца являются гетероатомами, выбранными из О, N и S, причем указанная карбоциклическая или гетероциклическая группа возможно содержит один или два заместителя R;Rвыбран из водорода и группы X-R;X представляет собой Cалкандиил, причем один атом углерода Салкандиила может быть необязательно связан с группой-СН-СН- с образованием циклопропан-1,1-диила, или два соседних атома углерода Cалкандиила могут быть необязательно связаны с группой -(СН), где n равен от 1 до 5, с образованием С-циклоалкан-1,2-диила;Rпредставляет собой 3-10-членное моноциклическое или бициклическое карбоциклическое или гетероциклическое кольцо, содержащее 0, 1, 2 или 3 гетероатома в кольце, выбранные из N, О и S, и возможно содержащее один или более заместителей R;Rвыбран из водорода и заместителя R;Rвыбран из следующего: галоген; циано; Салкил, возможно содержащи

Claims (20)

1. Соединение формулы (1):
Figure 00000001
или соль, N-оксид, таутомер или стереоизомер указанного соединения, где:
А представляет собой СН или азот;
Е представляет собой СН или азот;
R1 выбран из следующего:
- ациклическая C1-8 углеводородная группа, возможно содержащая один или два заместителя R6, причем один атом углерода в ациклической C1-8 углеводородной группе может быть необязательно заменен гетероатомом или группой, выбранными из О, S, NRc, S(O) и SO2, или два соседних атома углерода в ациклической d.8 углеводородной группе могут быть необязательно заменены группой, выбранной из CONRc, NRcCO, NRcSO2 и SO2NRc, при условии, что в каждом случае в ациклической C1-8 углеводородной группе сохраняется по меньшей мере один атом углерода; и
- моноциклическая карбоциклическая или гетероциклическая группа, содержащая от 3 до 7 членов кольца, из которых 0, 1, 2, 3 или 4 членов кольца являются гетероатомами, выбранными из О, N и S, причем указанная карбоциклическая или гетероциклическая группа возможно содержит один или два заместителя R7a;
R2 выбран из водорода и группы X-R8;
X представляет собой C1-8 алкандиил, причем один атом углерода С1-8 алкандиила может быть необязательно связан с группой-СН2-СН2- с образованием циклопропан-1,1-диила, или два соседних атома углерода C1-8 алкандиила могут быть необязательно связаны с группой -(СН2)n, где n равен от 1 до 5, с образованием С3-7-циклоалкан-1,2-диила;
R3 представляет собой 3-10-членное моноциклическое или бициклическое карбоциклическое или гетероциклическое кольцо, содержащее 0, 1, 2 или 3 гетероатома в кольце, выбранные из N, О и S, и возможно содержащее один или более заместителей R13;
R4 выбран из водорода и заместителя R4a;
R4a выбран из следующего: галоген; циано; С1-4алкил, возможно содержащий в качестве заместителей один или более атомов фтора; С1-4алкокси, возможно содержащий в качестве заместителей один или более атомов фтора; гидрокси-С1-4 алкил; и С1-2алкокси-С1-4алкил;
R5 выбран из водорода и заместителя R5a;
R5a выбран из следующего: C1-2алкил, возможно содержащий в качестве заместителей один или более атомов фтора; С1-3алкокси, возможно содержащий в качестве заместителей один или более атомов фтора; галоген; циклопропил; и циано;
R6 выбран из следующего: гидрокси; фтор; карбамоил; моно- или ди-С1-4 алкилкарбамоил; нитро; амино; моно- или ди-С1-4алкиламино; моноциклическая карбоциклическая или гетероциклическая группа, содержащая от 3 до 7 членов кольца, из которых 0, 1 или 2 гетероатома кольца выбраны из О, N и S, где указанная карбоциклическая или гетероциклическая группа возможно содержит один или два заместителя R7b;
R7a и R7b каждый независимо выбран из следующего: (=O); (=S); амино; галоген; циано; гидрокси; С1-4алкил; гидрокси-С1-4алкил; амино-С1-4 алкил; моно- и ди-С1-4алкиламино-С1-4алкил;
R8 выбран из следующего: гидрокси-группы и C(=O)NR10R11; при условии, что если R8 представляет собой гидрокси, между гидрокси-группой и атомом азота, к которому присоединен X, располагаются по меньшей мере три атома углерода подряд;
R10 выбран из водорода и C1-4алкила;
R11 выбран из следующего: водород; амино-С2-4 алкил и гидрокси-С2-4 алкил;
R13 выбран из следующего: галоген; циано; (=O); (=S); нитро; CH=NOH; и группа Ra-Rb;
Ra представляет собой связь, О, СО, Х1С(Х2), С(Х2)Х1, Х1С(Х2)Х1, S, SO, SO2, NRC, SO2NRc или NRcSO2;
Rb представляет собой водород, циклическую группу Rd; или ациклическую C1-8 углеводородную группу, возможно содержащую один или более заместителей, выбранных из гидрокси, оксо, галогена, циано, нитро, карбокси, амино, моно- или ди-C1-4 алкиламино и циклической группы Rd; причем один или два, но не все атомы углерода в ациклической C1-8 углеводородной группе могут быть необязательно заменены на О, S, SO, SO2, NRc, Х1С(Х2), С(Х2)Х1 или Х1С(Х2)Х1; SO2NRc или NRcSO2;
циклическая группа Rd представляет собой моноциклическую карбоциклическую или гетероциклическую группу, содержащую от 3 до 7 членов кольца, из которых 0, 1, 2 или 3 гетероатома кольца выбраны из О, N и S и их окисленных форм, причем карбоциклическая или гетероциклическая группа возможно содержит один или более заместителей, выбранных из R14;
R14 выбран из оксо; галогена; циано; и Ra-Re;
Re представляет собой водород или ациклическая C1-8 углеводородную группу, возможно содержащую один или более заместителей, выбранных из следующих: фенил; гидрокси; оксо; галоген; циано; карбокси; амино; моно- или ди-С1-4алкиламино; причем один или два, но не все атомы углерода в ациклической C1-8 углеводородной группе могут быть необязательно заменены на О, S, SO, SO2, NRc, Х1С(Х2), С(Х2)Х1 или Х1С(Х2)Х1; SO2NRc или NRcSO2;
X1 представляет собой О или NRc;
X2 представляет собой =O или =NRc; и
Rc представляет собой водород или алкил;
но за исключением соединений 1-(3-бензоилфенил)-этиламин и 1-(3-фуран-2-илкарбонилфенил)-этиламин.
2. Соединение по п. 1, отличающееся тем, что А представляет собой СН, и Е представляет собой СН.
3. Соединение по п. 1 или 2, где R2 представляет собой X-R8.
4. Соединение по п. 1 или 2, где R2 представляет собой водород.
5. Соединение по п. 3, где X представляет собой группу АА:
Figure 00000002
где "b" представляет собой точку присоединения к R8, и "а" представляет собой точку присоединения к атому азота бензила.
6. Соединение по п. 1, где R8 представляет собой C(=O)NH2.
7. Соединение по п. 1, где R1 представляет собой этил или циклопропил.
8. Соединение по п. 1, где R3 выбран из фенила и пиридила, каждый из которых содержит один или более заместителей R13.
9. Соединение по п. 1, где R13 представляет собой амино.
10. Соединение по п. 1, имеющее изомерную форму (1а):
Figure 00000003
или соль, N-оксил или таутомер указанного соединения, где:
А представляет собой СН;
Е представляет собой СН;
R1 представляет собой этил или циклопропил;
R2 представляет собой X-R8; где X представляет собой -*СН(СН3)СН2-, и звездочка обозначает хиральный центр, который находится в S-конфигурации;
R8 представляет собой C(=O)NR10R11 где R10 и R11 оба являются водород;
R4 представляет собой фтор;
R5 представляет собой хлор; и
R3 представляет собой пиридил, сожержащий один заместитель, который представляет собой группу NH2.
11. Соединение по п. 1, имеющее формулу (7):
Figure 00000004
или соль, N-оксид, таутомер или стереоизомер указанного соединения, где:
R1b выбран из следующего: С1-4алкил, аллил и циклопропил;
R2b выбран из водорода и группы Xb-R8b;
Xb представляет собой С1-5 алкандиил, где один атом углерода С1-4алкандиила может быть необязательно связан с группой -СН2-СН2- с образованием циклопропан-1,1-диила, или два соседних атома углерода С1-4алкандиила могут быть необязательно связаны с группой -СН2-СН2-СН2- с образованием циклопентан-1,2-диила;
R3b представляет собой карбоциклическое или гетероциклическое кольцо, выбранное из следующих: фенил, пиридил, 1-оксипиридил, пиридонил, пиразинил, пиримидинил, пиразинил, пиразолил, изотиазолил, тиазолил, изоксазолил, пиридооксазинонил и дигидробензоксазинил, каждый из которых возможно содержит один или более заместителей R13b;
R4b представляет собой галоген;
R5b выбран из следующего: галоген; гидрокси; С1-2алкил; С1-2алкокси; дифторметокси; трифторметокси;
R8b выбран из гидрокси и C(=O)NHR11b; при условии, что если R8b представляет собой гидрокси, то между гидрокси-группой и атомом азота, к которому присоединен Хb, располагаются по меньшей мере два атома углерода подряд;
R11b выбран из водорода и амино-С2-4алкил; и
R13b выбран из следующего: галоген, циано; гидрокси, C1-4 алкил, оксо, C1-4алкокси, гидрокси-С1-4 алкил, С1-4ацилокси-С1-4 алкил, С1-4 алкилсульфанил, амино, моно-C1-4 алкиламино, ди-С1-4 алкиламино, пиразолил, С1-4 алкоксикарбонилпиразолил, гидрокси-С1-4 алкил-пиразолил, карбокси и карбамоил.
12. Соединение по п. 1, имеющее формулу (8):
Figure 00000005
или соль, N-оксид, таутомер или стереоизомер указанного соединения,
где R11 выбран из водорода, амино-С2-4алкила и гидрокси-С2-4алкила;
X выбран из следующего: -(СН2)Р-, (CH2)q-CH(Alk)-(CH2)r, -CH(Alk)-W-, -(CH2)rC(CH3)2-(СН2)t- и -(CH2)t-W-(CH2)u-, где W представляет собой циклопропан-1,1-диил или циклопентан-1,2-диил; каждый Alk независимо выбран из метила, этила и изопропила; p равен 1, 2 или 3; q равен 0 или 1; r равен 0 или 1; t равен 0 или 1, и u равен 0 или 1; при условии, что общее число атомов углерода, содержащихся в X, за исключением атомомв углерода в любой присутствующей циклопропан-1,1-диильной группе или циклопентан-1,2-диильной группе, не превосходит 8;
R1 выбран из следующего: этил, пропил, циклопропил, циклопропилметил проп-2-ен-1-ил;
R5a выбран из следующего: фтор, хлор, метил и метокси;
R3 выбран из следующего: фенил, пиридил, пиразинил, пиримидинил, изоксазолил, изотиазолил, пиразолил, 3,4-дигидро-пиридооксазин и 3,4-дигидробензоксазин, каждый из которых является незамещенным или содержит один или два заместителя R13; и
R13 выбран из следующего: галоген, циано, гидрокси, С1-4алкокси, С1-4 алкил, гидрокси-С1-4 алкил, амино, моно-C1-4 алкиламино, ди-С1-4 алкиламино, оксо, оксидо, пиразолил, гидрокси-С1-4 алкил-пиразолил, карбокси и карбамоил.
13. Соединение по п. 1, имеющее формулу (9):
Figure 00000006
или соль, N-оксид, таутомер или стереоизомер указанного соединения,
где R17 выбран из этила и циклопропила; R18 выбран из следующего: амино и гидроксиметил; Е представляет собой N или C-R19; и R19 выбран из водорода, метила и хлора.
14. Соединение по п. 1, которое выбрано из
(3S)-3-{[(1R)-1-(3-бензоил-4-хлор-2-фторфенил)пропил]амино}бутанамида;
(3S)-3-{[(1R)-1-{3-[(6-аминопиридин-3-ил)карбонил]-4-хлор-2-фторфенил}пропил]-амино}бутанамида;
(3S)-3-{[(R)-{3-[(6-aминoпиpидин-3-ил)кapбoнил]-4-xлop-2-фтopфeнил}(циклoпpoпил)-метил]амино}бутанамида;
(3S)-3-{[(R)-{3-[(4-амино-3-хлорфенил)карбонил]-4-хлор-2-фторфенил}-(циклопропил)метил]-амино}бутанамида; и
(3S)-3-{[(R)-{3-[(4-амино-3-метилфенил)карбонил]-4-хлор-2-фторфенил}-(циклопропил)метил]-амино}бутанамида; и их солей.
15. Фармацевтическая композиция, содержащая соединение согласно любому из пп. 1-14 и фармацевтически приемлемое вспомогательное вещество.
16. Применение соединения по любому из пп. 1-14 в медицине; например, для применения в профилактике или лечении инфекции, вызванной вирусом гепатита С (HCV, ВГС).
17. Комбинация соединения по любому из пп. 1-14 и дополнительного агента против вируса гепатита С.
18. Комбинация соединения по любому из пп. 1-14 с по меньшей мере одним (например, 1, 2, 3 или 4, или более предпочтительно 1, 2 или 3, и наиболее предпочтительно от 2 до 3) другимтерапевтическим агентом, выбранным из (а) интерферонов; (b) рибавирина и его аналогов; (с) других ингибиторов протеазы NS3 ВГС; (d) ингибитора альфа-глюкозидазы 1; (е) гепатопротекторов; (f) нуклеозидных или нуклеотидных ингибиторов полимеразы NS5B ВГС; (g) ненуклеозидных ингибиторов полимеразы NS5B ВГС; (h) ингибиторов NS5A ВГС; (i) агонистов TLR-7; (j) ингибиторов циклофиллина; (k) ингибиторов IRES ВГС; (I) средств. улучшающих фармакокинетические свойства; (m) имменоглобулинов; (n) иммуномодуляторов; (о) противовоспалительных агентов; (p) антибиотиков; (q) ингибиторов геликазы NS3 ВГС; (r) антагонистов NS4a ВГС; (s) связывающих ингибиторов NS4b ВГС; (t) ингибиторов p7 ВГС; (u) ингибиторов кора ВГС; и (v) ингибиторов проникновения ВГС в клетку; (w) ингибиторов диацилглицеринацилтрансферазы 1 типа(DGAT-1).
19. Комбинация соединения по любому из пп. 1-14 с противораковым лекарственным средством, эффективая для лечения гепатоцеллюлярной карциномы.
20. Способ получения соединения формулы (1), определенного в любом из пп. 1-14, который включает:
(a) в случае, если необходимо получить соединение формулы (1), где R2 представляет собой водород, реакцию соединения формулы (10):
Figure 00000007
где PG представляет собой защитную группу, такую как группа трет-бутилоксикарбонил (Воc), с основным реагентом, таким как алкиллитий (например, бутиллитий), с последующей реакцией с соединением формулы R3-C(=O)-LG, где LG представляет собой уходящую группу, такую как метокси- или этоксигруппа, или хлорид (т.е. хлорангидрид кислоты), с получением а соединения формулы: (11):
Figure 00000008
с последующим удалением защитной группы PG; или
(b) в случае, если необходимо получить соединение формулы (1), где R2 представляет собой водород, окисление соединения формулы (30):
Figure 00000009
с использованием подходящего окисляющего агента, такого как диоксид магния или периодинан Десса-Мартина, с последующим удалением защитной группы PG; или
(c) в случае, если необходимо получить соединение формулы (1), где R3 представляет собой аминопиридин или аминопиразин, реакцию соединения формулы (31), (32), (33), (34) или (35):
Figure 00000010
Figure 00000011
Figure 00000012
Figure 00000013
Figure 00000014
где R° представляет собой водород, и R13 представляет собой бром или хлор, с аммиаком с получением соответствующего соединения, где R13 представляет собой амино; или
(d) в случае, если необходимо получить соединение формулы (1), где R2 представляет собой X-R8, реакцию соединения формулы (1), где R2 представляет собой водород с алкилирующим агентом формулы LG1-X-R8, где LG1 представляет собой уходящую группу, обычно в присутствии основания; или
(e) в случае, если необходимо получить соединение формулы (1), где R2 представляет собой X-R8, реакцию соединения формулы (1), где R2 представляет собой водород с альдегидом или кетоном X"-C(=0)-X'-R8, где X" и X' представляют собой остатки группы X; в присутствии восстанавливающего агента; или
(f) в случае, если необходимо получить соединение формулы (1), где R8 представляет собой C(=O)NR10R11, реакцию соединения формулы (1), где R2 представляет собой водород, с соединением X'"-C(=O)NR10R11 или Х"'-С(=0)Ма, где Ма представляет собой маскированную аминогруппу или предшественник аминогруппы, и X'" содержит двойную смесь, сопряженную с карбонильной группой фрагмента C(=O)NR10R11; или
(g) в случае, если необходимо получить соединение формулы (1), где R2 представляет собой X-R8, и R8 представляет собой C(=O)NR10R11, реакцию соединения-предшественника, содержащего группу X-R8prec, где R8prec представляет сбой группу-предшественника группы C(=O)NR10R11 (такую как группа карбоновой кислоты, или циано-группа или сложноэфирная группа) с реагентом, подходящим для превращения R8prec в группу C(=O)NR10R11; с последующим удалением всех еще присутствующих групп PG; и
(h) возможно превращение одного соединения формулы (1) в другое соединение формулы (1).
RU2014113973/04A 2011-11-01 2012-10-31 Фармацевтические соединения RU2014113973A (ru)

Applications Claiming Priority (11)

Application Number Priority Date Filing Date Title
US201161554421P 2011-11-01 2011-11-01
US201161554237P 2011-11-01 2011-11-01
GBGB1118875.2A GB201118875D0 (en) 2011-11-01 2011-11-01 Pharmaceutical compounds
US61/554,421 2011-11-01
GB1118874.5 2011-11-01
GB1118875.2 2011-11-01
US61/554,237 2011-11-01
GB201118874A GB201118874D0 (en) 2011-11-01 2011-11-01 Pharmaceutical compounds
US201261625925P 2012-04-18 2012-04-18
US61/625,925 2012-04-18
PCT/EP2012/071573 WO2013064543A1 (en) 2011-11-01 2012-10-31 Pharmaceutical compounds

Publications (1)

Publication Number Publication Date
RU2014113973A true RU2014113973A (ru) 2015-12-10

Family

ID=48191401

Family Applications (1)

Application Number Title Priority Date Filing Date
RU2014113973/04A RU2014113973A (ru) 2011-11-01 2012-10-31 Фармацевтические соединения

Country Status (18)

Country Link
US (1) US9145354B2 (ru)
EP (1) EP2773615A1 (ru)
JP (1) JP2015501316A (ru)
KR (1) KR20140102200A (ru)
CN (1) CN104039766A (ru)
AR (1) AR088596A1 (ru)
AU (1) AU2012331190A1 (ru)
BR (1) BR112014009319A2 (ru)
CA (1) CA2853008A1 (ru)
HK (1) HK1201534A1 (ru)
IL (1) IL232392A0 (ru)
MX (1) MX2014005228A (ru)
PH (1) PH12014500669A1 (ru)
RU (1) RU2014113973A (ru)
SG (1) SG11201400872YA (ru)
TW (1) TW201329025A (ru)
WO (1) WO2013064543A1 (ru)
ZA (1) ZA201403832B (ru)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2788343B1 (en) 2011-12-11 2018-02-28 Viamet Pharmaceuticals (NC), Inc. Metalloenzyme inhibitor compounds
AU2014227849A1 (en) * 2013-03-15 2015-10-01 Achillion Pharmaceuticals, Inc. Sovaprevir polymorphs and methods of manufacture thereof
CN104569276B (zh) * 2014-12-25 2016-04-20 广东东阳光药业有限公司 一种用hplc测定索氟布韦片有关物质的方法
KR101658593B1 (ko) * 2015-04-22 2016-09-21 서울대학교산학협력단 Pi4k 동위효소 저해제를 유효성분으로 포함하는 방사선 민감성 증진용 조성물
KR20180011843A (ko) 2015-06-11 2018-02-02 바실리어 파마슈티카 인터내셔널 리미티드 유출-펌프 억제제 및 이의 치료적 용도
MX391538B (es) 2015-09-18 2025-03-21 Mycovia Pharmaceuticals Inc Proceso de compuesto antifungico.
PE20181893A1 (es) * 2016-02-15 2018-12-11 Sanofi Sa Nuevos compuestos de 6,7-dihidro-5h-benzo[7]anuleno sustituidos, procesos para su preparacion y usos terapeuticos de los mismos
EP3474845B1 (en) * 2016-06-27 2024-03-20 ChemoCentryx, Inc. Immunomodulator compounds
WO2020036869A1 (en) 2018-08-16 2020-02-20 Emd Millipore Corporation Closed bioprocessing device

Family Cites Families (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3766475D1 (de) 1986-11-03 1991-01-10 Merck & Co Inc 4-(benzoyl)thiophen(oder furan)-sulfonamid und derivate fuer die aeusserliche behandlung von erhoehtem augeninnendruck.
MY104343A (en) 1987-11-23 1994-03-31 Janssen Pharmaceutica Nv Novel pyridizinamine deravatives
US5212320A (en) * 1990-05-21 1993-05-18 Fujisawa Pharmaceutical Co., Ltd. Indole derivatives and their use for testosterone 5-alpha-reductase-mediated diseases
GB9011335D0 (en) * 1990-05-21 1990-07-11 Fujisawa Pharmaceutical Co Indolebutyric acid derivatives and process for preparation thereof
US6011068A (en) 1991-08-23 2000-01-04 Nps Pharmaceuticals, Inc. Calcium receptor-active molecules
DE4241632A1 (de) 1992-12-10 1994-06-16 Thomae Gmbh Dr K Carbonsäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung
GB9511694D0 (en) 1995-06-09 1995-08-02 Fujisawa Pharmaceutical Co Benzamide derivatives
US6204293B1 (en) 1995-11-06 2001-03-20 University Of Pittsburgh Inhibitors of protein isoprenyl transferases
AUPO395396A0 (en) 1996-12-02 1997-01-02 Fujisawa Pharmaceutical Co., Ltd. Benzamide derivatives
WO1998050031A1 (en) 1997-05-07 1998-11-12 University Of Pittsburgh Inhibitors of protein isoprenyl transferases
ES2352739T3 (es) 1997-11-21 2011-02-22 Purdue Neuroscience Company 2-aminoacetamidas sustituidas y el uso de las mismas.
US6586475B1 (en) 1998-11-20 2003-07-01 Takeda Chemical Industries, Ltd. β-amyloid protein production/secretion inhibitors
HU229404B1 (en) 1998-12-23 2013-12-30 Janssen Pharmaceutica Nv 1,2-annelated quinoline derivatives
AU7446900A (en) 1999-09-28 2001-04-30 Nihon Nohyaku Co., Ltd. Thioalkylamine derivatives and process for the preparation thereof
US20040110743A1 (en) 2000-05-19 2004-06-10 Masaomi Miyamato -Secretase inhibitors
US20050010048A1 (en) 2000-10-12 2005-01-13 Linghang Zhuang Aza-and polyaza-naphthalenly ketones useful as hiv integrase inhibitors
US7507767B2 (en) 2001-02-08 2009-03-24 Schering Corporation Cannabinoid receptor ligands
US7067539B2 (en) 2001-02-08 2006-06-27 Schering Corporation Cannabinoid receptor ligands
EP1395571A1 (en) * 2001-06-11 2004-03-10 Shire Biochem Inc. Compounds and methods for the treatment or prevention of flavivirus infections
US20030187026A1 (en) 2001-12-13 2003-10-02 Qun Li Kinase inhibitors
JP4522851B2 (ja) 2002-05-24 2010-08-11 バイエル・クロツプサイエンス・アクチエンゲゼルシヤフト チオアルキルアミン誘導体の調製方法
ZA200510137B (en) 2003-07-24 2007-04-25 Leo Pharma As Novel aminobenzophenone compounds
DE10359791A1 (de) 2003-12-19 2005-07-21 Bayer Healthcare Ag Substituierte Thiophene
WO2005123671A1 (ja) 2004-06-22 2005-12-29 Taisho Pharmaceutical Co., Ltd. ピロール誘導体
BRPI0615131A2 (pt) 2005-08-24 2011-05-03 Bayer Cropscience Ag preparação de tioalquilaminas com rendimentos elevados
WO2007022901A1 (en) 2005-08-24 2007-03-01 Bayer Cropscience Ag Preparation of thioalkylamines using chlorosulfonic acid
RU2458051C2 (ru) 2005-11-24 2012-08-10 ДОМПЕ ФА.Р.МА С.п.А. (r)-арилалкиламинопроизводные и содержащие их фармацевтические композиции
SI1957073T1 (sl) 2005-12-05 2014-08-29 Otsuka Pharmaceutical Co., Ltd. A Corporation Organized Under The Laws Of Japan Medicinsko zdravilo
UA95978C2 (ru) 2006-10-02 2011-09-26 Оцука Фармас'Ютікел Ко., Лтд. Ингибитор активации stat3/5
WO2009009041A2 (en) 2007-07-06 2009-01-15 Kinex Pharmaceuticals, Llc Compositions and methods for modulating a kinase cascade
WO2009143018A2 (en) 2008-05-19 2009-11-26 Plexxikon, Inc. Compounds and methods for kinase modulation, and indications therefor
JP5767965B2 (ja) 2008-06-10 2015-08-26 プレキシコン インコーポレーテッドＰｌｅｘｘｉｋｏｎ Ｉｎｃ． キナーゼを調節する５ｈ−ピロロ［２，３−ｂ］ピラジン誘導体、およびその適応症
ES2383273T3 (es) 2008-07-23 2012-06-19 F. Hoffmann-La Roche Ag Compuestos heterocíclicos antivíricos
GB2467561A (en) 2009-02-06 2010-08-11 Summit Corp Plc Dual calpain-ROS inhibitors

Also Published As

Publication number Publication date
CN104039766A (zh) 2014-09-10
HK1201534A1 (en) 2015-09-04
AR088596A1 (es) 2014-06-18
WO2013064543A1 (en) 2013-05-10
SG11201400872YA (en) 2014-08-28
PH12014500669A1 (en) 2014-05-12
TW201329025A (zh) 2013-07-16
MX2014005228A (es) 2015-07-06
EP2773615A1 (en) 2014-09-10
CA2853008A1 (en) 2013-05-10
AU2012331190A1 (en) 2014-04-10
KR20140102200A (ko) 2014-08-21
ZA201403832B (en) 2016-02-24
IL232392A0 (en) 2014-06-30
BR112014009319A2 (pt) 2017-05-30
US20150051199A1 (en) 2015-02-19
JP2015501316A (ja) 2015-01-15
US9145354B2 (en) 2015-09-29

Similar Documents

Publication Publication Date Title
RU2014113973A (ru) Фармацевтические соединения
JP6388991B2 (ja) キナーゼ阻害剤としてのアミノヘテロアリールベンズアミド
RU2768827C2 (ru) Модуляторы хемокинового рецептора и их применение
JP6478991B2 (ja) Ｉｄｏ阻害剤
JP4914355B2 (ja) Ｃ型肝炎インヒビターペプチド類似体
JP2025503641A (ja) Ｒａｓ阻害剤
WO2019177902A1 (en) Modulators of btk proteolysis and methods of use
TW201033196A (en) Inhibitors of HCV NS5A
IL285177B2 (en) Compounds and their use
RU2014103960A (ru) Гетероарилзамещенные пиразолопиридины и их применение в качестве стимуляторов растворимой гуанилатциклазы
JP2016512834A5 (ru)
BR112016008378B1 (pt) Compostos de quinolina seletivamente substituídos ou sal dos mesmos, e composição farmacêutica contendo os ditos compostos
RU2015148006A (ru) Дейтерированные нуклеозидные пролекарства, применимые для лечения hcv
EA013207B1 (ru) Ингибиторы вирусной полимеразы
WO2011075607A1 (en) Novel inhibitors of hepatitis c virus replication
JP2008504240A (ja) Ｃ型肝炎インヒビターペプチド類似体
RU2005110061A (ru) Замещенные пиперазины, (1,4)-диазепины и 2,5-диазабицикло(2,2,1)гептаны в качестве н1-и/или н3-антагонистов гистамина или обратных н3-антагонистов гистамина
ES2558608T3 (es) Derivados hetero-bicíclicos como inhibidores del VHC
JP2013504604A (ja) ウイルスポリメラーゼ阻害剤としてのキナゾリノン誘導体
RU2015109064A (ru) Амиды азаиндолкарбоновых и азаиндолтиокарбоновых кислот в качестве инсектицитов и акарицидов
TW201019950A (en) Therapeutic antiviral peptides
BR112021011861A2 (pt) Inibidores da proteína de ativação de fibroblastos
JP2016535769A5 (ru)
TW201307318A (zh) 二聚合之ｉａｐ抑制劑
CN105968101A (zh) 作为丙型肝炎抑制剂的化合物及其在药物中的应用

Legal Events

Date Code Title Description
FA93 Acknowledgement of application withdrawn (no request for examination)

Effective date: 20151102