RU2015102095A - 3-о-гетероарилингенол - Google Patents

3-о-гетероарилингенол Download PDF

Info

Publication number
RU2015102095A
RU2015102095A RU2015102095A RU2015102095A RU2015102095A RU 2015102095 A RU2015102095 A RU 2015102095A RU 2015102095 A RU2015102095 A RU 2015102095A RU 2015102095 A RU2015102095 A RU 2015102095A RU 2015102095 A RU2015102095 A RU 2015102095A
Authority
RU
Russia
Prior art keywords
ingenol
acetonide
pyridyl
group
neoplasia
Prior art date
Application number
RU2015102095A
Other languages
English (en)
Inventor
Сифу Лян
Томас ХЕГБЕРГ
Бьярнэ НОРРЕМАРК
Кристоффер МОНССОН
Карстен РЮТТЕРСГОРД
Гуннар ГРУЭ-СЕРЕНСЕН
Original Assignee
Лео Лэборетериз 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
Application filed by Лео Лэборетериз Лимитед filed Critical Лео Лэборетериз Лимитед
Publication of RU2015102095A publication Critical patent/RU2015102095A/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
    • C07D213/78—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
    • C07D213/04—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
    • C07D213/85—Nitriles in position 3
    • 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
    • A61K31/415—1,2-Diazoles
    • A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
    • 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
    • A61K31/4164—1,3-Diazoles
    • 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
    • A61K31/42—Oxazoles
    • A61K31/423—Oxazoles condensed with carbocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—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
    • A61K31/4245—Oxadiazoles
    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4355—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having oxygen as a ring hetero atom
    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4365—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
    • 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
    • A61K31/435—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
    • A61K31/47—Quinolines; Isoquinolines
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • 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
    • A61K31/495—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
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • 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
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
    • A61K8/4946—Imidazoles or their condensed derivatives, e.g. benzimidazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
    • A61K8/4953—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom containing pyrimidine ring derivatives, e.g. minoxidil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4986—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with sulfur as the only hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • 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
    • A61P17/12—Keratolytics, e.g. wart or anti-corn preparations
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
    • 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
    • C07D213/69—Two or more oxygen 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
    • C07D215/20—Oxygen atoms
    • C07D215/22—Oxygen atoms attached in position 2 or 4
    • 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
    • C07D215/20—Oxygen atoms
    • C07D215/22—Oxygen atoms attached in position 2 or 4
    • C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 nitrogen-containing ring
    • C07D217/24—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
    • C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
    • 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
    • C07D233/66—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 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
    • C07D233/70—One oxygen atom
    • 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
    • C07D239/34—One oxygen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/20—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
    • C07D271/07—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Birds (AREA)
  • Dermatology (AREA)
  • Gerontology & Geriatric Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Reproductive Health (AREA)
  • Endocrinology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Cosmetics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pyridine Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

1. Соединение общей формулы I,где Rпредставляет собой гетероарил и где Rнеобязательно замещен одним или более заместителями, независимо выбранными из R;где Rпредставляет собой циано или галоген;или Rпредставляет собой (C-C) алкил, (С-С) алкенил, (C-С)алкокси, (С-С) циклоалкил, гало (C-C) алкилокси, гетероциклоалкил, арил или гетероарил; где упомянутый (С-С) алкил необязательно замещен одним или более заместителями, независимо выбранными из группы, включающей галоген, циано, гидроксил и оксо;или Rпредставляет собой -NRCOR, -CONRR, -COOR, -OCOR, -OR, -OCONRR, -NRCOOR, -NRSOR, -SONRR, -SOR, -S(O)Rили -NRR;где Rи Rкаждый независимо выбран из группы, включающей водород, (С-С) алкил, гало (C-C) алкил, гидрокси (С-С) алкил, циано (C-C) алкил, арил, гетероарил, (С-С) циклоалкил и гетероциклоалкил;или два соседних Rсвязаны вместе с атомами углерода или азота, к которым они присоединены с образованием 5-7-членного неароматического карбоциклического или гетероциклического кольца;и его фармацевтически приемлемые соли, гидраты, сольваты или фармацевтически приемлемые и физиологически расщепляемые сложные эфиры.2. Соединение по п. 1, гдеRпредставляет собой гетероарил; где упомянутый гетероарил необязательно замещен одним или более заместителями, независимо выбранными из R; и где упомянутый гетероарил выбран из группы, включающейгде X, Х, Хи Хкаждый независимо выбран из группы, включающей С, СН, N, NH, S и О;и где Y, Y, Y, Y, Y, Y, Y, Y, Yи Yкаждый независимо выбран из группы, включающей С, СН и N.3. Соединение по п. 2, гдеRпредставляет собой Gи где по меньшей мере один из Xили Хвыбран из группы, включающей N, NH, S и О; илиRпредставляет собой G, и где по меньшей мере один из Yили Yпредставляет собой N; илиRпредставляет собой G, и где присоединение к 3-O-ингенолу осуществляется через Xили Х, и где Хвыбран из группы, включающей N, NH, S и

Claims (28)

1. Соединение общей формулы I
Figure 00000001
,
где R1 представляет собой гетероарил и где R1 необязательно замещен одним или более заместителями, независимо выбранными из R2;
где R2 представляет собой циано или галоген;
или R2 представляет собой (C1-C6) алкил, (С2-С6) алкенил, (C1-С6)алкокси, (С3-С6) циклоалкил, гало (C1-C6) алкилокси, гетероциклоалкил, арил или гетероарил; где упомянутый (С1-С6) алкил необязательно замещен одним или более заместителями, независимо выбранными из группы, включающей галоген, циано, гидроксил и оксо;
или R2 представляет собой -NRaCORb, -CONRaRb, -COORa, -OCORa, -ORa, -OCONRaRb, -NRaCOORb, -NRaSO2Rb, -SO2NRaRb, -SO2Ra, -S(O)Ra или -NRaRb;
где Ra и Rb каждый независимо выбран из группы, включающей водород, (С1-С4) алкил, гало (C1-C4) алкил, гидрокси (С1-С4) алкил, циано (C1-C4) алкил, арил, гетероарил, (С3-С6) циклоалкил и гетероциклоалкил;
или два соседних R2 связаны вместе с атомами углерода или азота, к которым они присоединены с образованием 5-7-членного неароматического карбоциклического или гетероциклического кольца;
и его фармацевтически приемлемые соли, гидраты, сольваты или фармацевтически приемлемые и физиологически расщепляемые сложные эфиры.
2. Соединение по п. 1, где
R1 представляет собой гетероарил; где упомянутый гетероарил необязательно замещен одним или более заместителями, независимо выбранными из R2; и где упомянутый гетероарил выбран из группы, включающей
Figure 00000002
где X1, Х2, Х3 и Х4 каждый независимо выбран из группы, включающей С, СН, N, NH, S и О;
и где Y1, Y2, Y3, Y4, Y5, Y6, Y7, Y8, Y9 и Y10 каждый независимо выбран из группы, включающей С, СН и N.
3. Соединение по п. 2, где
R1 представляет собой G1 и где по меньшей мере один из X1 или Х4 выбран из группы, включающей N, NH, S и О; или
R1 представляет собой G2, и где по меньшей мере один из Y1 или Y5 представляет собой N; или
R1 представляет собой G3, и где присоединение к 3-O-ингенолу осуществляется через X1 или Х3, и где Х2 выбран из группы, включающей N, NH, S и О;
или
R1 представляет собой G3, и где присоединение к 3-O-ингенолу осуществляется через Х2, и где по меньшей мере один из Х1 и Х3, выбран из группы, включающей N, NH, S и О;
или
R1 представляет собой G4, и где присоединение к 3-O-ингенолу осуществляется через Y1, и где Y2 представляет собой N;
или
R1 представляет собой G4, и где присоединение к 3-О-ингенолу осуществляется через Y2, и где по меньшей мере один из Υ1 и Υ3 представляет собой Ν;
или
R1 представляет собой G5, и где присоединение к 3-О-ингенолу осуществляется через Υ1 и где Y2 представляет собой Ν; или
R1 представляет собой G5, и где присоединение к 3-О-ингенолу осуществляется через Y2, и где по меньшей мере один из Υ1 и Y3 представляет собой N.
4. Соединение по п. 2, 3, где
R1 представляет собой G1, и где один из Χ1 или Х4 выбран из группы, включающей Ν, ΝΗ, S и О, и где другой из Χ1 или Х4 замещен R2;
или
R1 представляет собой G2, и где один из Υ1 или Υ5 представляет собой Ν, и где другой из Υ1 или Υ5 замещен R2; или
R1 представляет собой G3, и где присоединение к 3-О-ингенолу осуществляется через Χ1 или Х3, и где Х2 выбран из группы, включающей Ν, ΝΗ, S и О;
или
R1 представляет собой G4, и где присоединение к 3-О-ингенолу осуществляется через Υ1, и где Υ2 представляет собой Ν; или
R1 представляет собой G5, и где присоединение к 3-О-ингенолу осуществляется через Υ1, и где Υ2 представляет собой N.
5. Соединение по пп. 1-3, где R1 представляет собой оксазолил, изоксазолил, тиазолил, изотиазолил, имидазолил, пиразолил, пиридил, пиримидинил, пиразинил, пиридазинил, триазинил, изохинолинил, бензоксазолил, индазолил, тиенопиридил, фуропиридил или оксадиазолил.
6. Соединение по пп. 1-3, где R2 представляет собой галоген, циано, (С1-С4) алкил, гало (С1-С4) алкил, (С2-С6) алкенил, (С1-С6)алкокси или (С3-С6) циклоалкил.
7. Соединение по пп. 1-3, где R2 представляет собой метил, трифторметил, трифторэтил, пропенил, бром, хлор, фтор, циано, метокси, изопропил, циклопентил, дифторэтил или фторэтил.
8. Соединение по пп. 1-3, выбранное из группы, включающей
3-O-(6-Хлор-5-метилпиримидин-4-ил)ингенол,
3-O-(1,2-Бензоксазол-3-ил)ингенол,
3-O-(5-(Трифторметил)-2-пиридил)ингенол,
3-O-(5-Аллил-6-хлорпиримидин-4-ил)ингенол,
3-O-(3-Формил-2-пиридил)ингенол,
3-O-(2-Пиридил)ингенол,
3-O-(1-Метилиндазол-3-ил)ингенол,
3-O-(1-Метилимидазол-2-ил)ингенол,
3-O-(1-Аллилимидазол-2-ил)ингенол,
3-O-(5-(Трифторметил)пиримидин-2-ил)ингенол,
3-O-(4-Бром-2-пиридил)ингенол,
3-O-(3-Фтор-2-пиридил)ингенол,
3-O-(4-(Трифторметил)-2-пиридил)ингенол,
3-O-(4-(Трифторметил)пиримидин-2-ил)ингенол,
3-O-(3-Хлор-2-пиридил)ингенол,
3-O-(3-Циано-2-пиридил)ингенол,
3-O-(6-(Трифторметил)-2-пиридил)ингенол,
3-O-(3-(Трифторметил)-2-пиридил)ингенол,
3-O-(1-Изохинолил)ингенол,
3-O-(1-Циклопентилимидазол-2-ил)ингенол,
3-O-(1-(2,2-Дифторэтил)имидазол-2-ил)ингенол,
3-O-(1-(2-Фторэтил)имидазол-2-ил)ингенол,
3-O-(Тиено[2,3-е]пиридин-7-ил)ингенол,
3-O-(3-Метил-2-пиридил)ингенол,
3-O-(6-Хлор-1,2-бензоксазол-3-ил)ингенол,
3-O-(Фуро[3,2-е]пиридин-4-ил)ингенол,
3-O-(Тиено[3,2-е]пиридин-4-ил)ингенол,
3-O-(4-Фтор-1,2-бензоксазол-3-ил)ингенол,
3-O-(3-Метоксипиридин-2-ил)ингенол,
3-O-(5-Метокси-1,2-бензоксазол-3-ил)ингенол,
3-O-(5-Хлор-1,2-бензоксазол-3-ил)ингенол,
3-O-(6-Метокси-1,2-бензоксазол-3-ил)ингенол,
3-O-(5-Изопропил-1,2,4-оксадиазол-3-ил)ингенол
и его фармацевтически приемлемые соли, гидраты, сольваты или фармацевтически приемлемые и физиологически расщепляемые сложные эфиры.
9. Применение соединения по любому из пп. 1-8 в качестве лекарственного средства в терапии.
10. Применение соединения по любому из пп. 1-8 в лечении, предупреждении, улучшении или профилактике физиологических расстройств или заболеваний, связанных с гиперплазией, неоплазией или дисплазией.
11. Применение по п. 10, где расстройство или заболевание выбрано из кожных бородавок, генитальных бородавок, старческого кератоза, плоскоклеточного рака (ПКР), базальноклеточного рака (БКР), злокачественного лентиго, интраэпителиальной цервикальной неоплазии, интраэпителиальной анальной неоплазии или интраэпителиальной неоплазии вульвы.
12. Применение соединения по любому из пп. 1-8 в изготовлении фармацевтического средства.
13. Применение соединения по п. 12 в изготовлении лекарственного средства для лечения, облегчения или профилактики физиологических расстройств или заболеваний, связанных с гиперплазией, неоплазией или дисплазией.
14. Применение по п. 13, где расстройство или заболевание выбрано из кожных бородавок, генитальных бородавок, старческого кератоза, плоскоклеточного рака (ПКР), базальноклеточного рака (БКР), злокачественного лентиго, интраэпителиальной цервикальной неоплазии, интраэпителиальной анальной неоплазии или интраэпителиальной неоплазии вульвы.
15. Применение по п. 14, где расстройством или заболеванием является старческий кератоз.
16. Способ предупреждения, лечения, облегчения или профилактики физиологических расстройств или заболеваний, связанных с гиперплазией, неоплазией или дисплазией, включающий введение субъекту, нуждающемуся в этом, соединения по любому одному из пп. 1-8 необязательно вместе с фармацевтически приемлемым носителем или одним или более эксципиентами необязательно в комбинации с другими терапевтически активными соединениями.
17. Способ по п. 16, где расстройство или заболевание выбрано из кожных бородавок, генитальных бородавок, старческого кератоза, плоскоклеточного рака (ПКР), базальноклеточного рака (БКР), злокачественного лентиго, интраэпителиальной цервикальной неоплазии, интраэпителиальной анальной неоплазии или интраэпителиальной неоплазии вульвы.
18. Способ по п. 17, где расстройством или заболеванием является старческий кератоз.
19. Применение соединения по любому одному из пп. 1-8 в лечении или улучшении косметических показаний.
20. Применение по п. 19, где косметическое показание выбрано из фотоповрежденной кожи или себорейного кератоза.
21. Применение соединения по п. 12 в изготовлении лекарственного средства для лечения или облегчения косметических показаний.
22. Применение по п. 21, где косметическое показание выбрано из фотоповрежденной кожи или себорейного кератоза.
23. Способ лечения или облегчения косметических показаний, включающий введение субъекту, нуждающемуся в этом, соединения по любому одному из пп. 1-8 необязательно вместе с фармацевтически приемлемым носителем или одним или более эксципиентами необязательно в комбинации с другими терапевтически активными соединениями.
24. Способ по п. 23, где косметическое показание выбрано из фотоповрежденной кожи или себорейного кератоза.
25. Фармацевтическая композиция, содержащая соединение по любому одному из пп. 1-8 или его фармацевтически приемлемый стереоизомер, соль или in vivo гидролизируемый сложный эфир вместе с фармацевтически приемлемым носителем или эксципиентом.
26. Фармацевтическая композиция по п. 25, где композиция пригодна для местного применения.
27. Фармацевтическая композиция, содержащая соединение по любому одному из пп. 1-8 или его фармацевтически приемлемый стереоизомер, соль или in vivo гидролизируемый сложный эфир в комбинации с одним или более другими терапевтически активными агентами.
28. Соединение, выбранное из группы, включающей
3-O-(6-Хлор-5-метилпиримидин-4-ил)ингенол-5,20-ацетонид,
3-O-(1,2-Бензоксазол-3-ил)ингенол-5,20-ацетонид,
3-O-(5-(Трифторметил)-2-пиридил)ингенол-5,20-ацетонид,
3-O-(5-Аллил-6-хлорпиримидин-4-ил)ингенол-5,20-ацетонид,
3-O-(3-Формил-2-пиридил)ингенол-5,20-ацетонид,
3-O-(2-Пиридил)ингенол-5,20-ацетонид,
3-O-(1-Метилиндазол-3-ил)ингенол-5,20-ацетонид,
3-O-(1-Метилимидазол-2-ил)ингенол-5,20-ацетонид,
3-O-(1-Аллилимидазол-2-ил)ингенол-5,20-ацетонид,
3-O-(5-(Трифторметил)пиримидин-2-ил)ингенол-5,20-ацетонид,
3-O-(4-Бром-2-пиридил)ингенол-5,20-ацетонид,
3-O-(3-Фтор-2-пиридил)ингенол-5,20-ацетонид,
3-O-(4-(Трифторметил)-2-пиридил)ингенол-5,20-ацетонид,
3-O-(4-(Трифторметил)пиримидин-2-ил)ингенол-5,20-ацетонид,
3-O-(3-Хлор-2-пиридил)ингенол-5,20-ацетонид,
3-O-(3-Циано-2-пиридил)ингенол-5,20-ацетонид,
3-O-(6-(Трифторметил)-2-пиридил)ингенол-5,20-ацетонид,
3-O-(3 -(Трифторметил)-2-пиридил)ингенол-5,20-ацетонид,
3-O-(1-Изохинолил)ингенол-5,20-ацетонид,
3-O-(1-Циклопентилимидазол-2-ил)ингенол-5,20-ацетонид,
3-O-(1-(2,2-Дифторэтил)имидазол-2-ил)ингенол-5,20-ацетонид,
3-O-(1-(2-Фторэтил)имидазол-2-ил)ингенол-5,20-ацетонид,
3-O-(Тиено[2,3-е]пиридин-7-ил)ингенол-5,20-ацетонид,
3-O-(3-Метил-2-пиридил)ингенол-5,20-ацетонид,
3-O-(6-Хлор-1,2-бензоксазол-3-ил)ингенол-5,20-ацетонид,
3-O-(Фуро[3,2-с]пиридин-4-ил)ингенол-5,20-ацетонид,
3-O-(Тиено[3,2-е]пиридин-4-ил)ингенол-5,20-ацетонид,
3-O-(4-Фтор-1,2-бензоксазол-3-ил)ингенол-5,20-ацетонид,
3-O-(3-Метоксипиридин-2-ил)ингенол-5,20-ацетонид,
3-O-(5-Метокси-1,2-бензоксазол-3-ил)ингенол-5,20-ацетонид,
3-O-(5-Хлор-1,2-бензоксазол-3-ил)ингенол-5,20-ацетонид,
3-O-(6-Метокси-1,2-бензоксазол-3-ил)ингенол-5,20-ацетонид,
3-O-(5-Изопропил-1,2,4-оксадиазол-3-ил)ингенол-5,20-ацетонид.
RU2015102095A 2012-06-26 2013-06-21 3-о-гетероарилингенол RU2015102095A (ru)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201261664398P 2012-06-26 2012-06-26
US61/664,398 2012-06-26
US201361763206P 2013-02-11 2013-02-11
US61/763,206 2013-02-11
PCT/EP2013/062995 WO2014001215A2 (en) 2012-06-26 2013-06-21 3-o-heteroaryl-ingenol

Publications (1)

Publication Number Publication Date
RU2015102095A true RU2015102095A (ru) 2016-08-10

Family

ID=48874993

Family Applications (1)

Application Number Title Priority Date Filing Date
RU2015102095A RU2015102095A (ru) 2012-06-26 2013-06-21 3-о-гетероарилингенол

Country Status (22)

Country Link
US (1) US9422309B2 (ru)
EP (1) EP2864290B1 (ru)
JP (1) JP6216781B2 (ru)
KR (1) KR20150024928A (ru)
CN (1) CN104411685B (ru)
AU (1) AU2013283511B2 (ru)
BR (1) BR112014032244A2 (ru)
CA (1) CA2875461A1 (ru)
DK (1) DK2864290T3 (ru)
ES (1) ES2640612T3 (ru)
HK (1) HK1207624A1 (ru)
IL (1) IL235925A0 (ru)
IN (1) IN2014DN11023A (ru)
MX (1) MX2014015497A (ru)
MY (1) MY169215A (ru)
NZ (1) NZ702835A (ru)
PL (1) PL2864290T3 (ru)
PT (1) PT2864290T (ru)
RU (1) RU2015102095A (ru)
SG (1) SG11201408016XA (ru)
WO (1) WO2014001215A2 (ru)
ZA (1) ZA201409022B (ru)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015059574A1 (en) * 2013-10-25 2015-04-30 Leo Laboratories Limited A method for topically treating actinic keratosis on the trunk (except chest) or extremities with ingenol 3-(3,5-diethylisoxazole-4-carboxylate)
WO2016191835A1 (pt) * 2015-06-03 2016-12-08 Amazônia Fitomedicamentos Ltda. Método de preparação de ingenol-5,20-acetonida, método de preparação de 3-etinil-3-hidroxi-4.7.7-trimetilbiciclo[4.1.0] heptano-2-carbaldeído, método de preparação do composto 2,2-dimetil-4-etinil-5 -trifenilfosforanilideno-1,3-dioxano e composto intermediário
WO2017089300A1 (en) * 2015-11-27 2017-06-01 Leo Laboratories Limited 3-alkylamido-3-deoxy-ingenols
US10583140B2 (en) 2016-01-27 2020-03-10 Glaxosmithkline Intellectual Property Development Limited Ingenol analogs, pharmaceutical compositions and methods of use thereof
WO2017156350A1 (en) 2016-03-09 2017-09-14 K-Gen, Inc. Methods of cancer treatment

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2902506A1 (de) * 1979-01-23 1980-07-24 Deutsches Krebsforsch Verwendung von nicht oder nur gering irritierenden und/oder promovierenden diterpenalkoholen und von derivaten davon als antineoplastische mittel
AUPO864097A0 (en) 1997-08-19 1997-09-11 Peplin Pty Ltd Anti-cancer compounds
EP1838330A4 (en) * 2004-12-13 2010-07-07 Peplin Research Pty Ltd TREATMENT OF SOLID TUMORS
KR20080077625A (ko) * 2005-11-25 2008-08-25 페플린 리서치 피티이 리미티드 상처 치유 방법
GB0525680D0 (en) 2005-12-16 2006-01-25 Peplin Ltd Therapeutic compositions
MY154484A (en) * 2007-04-30 2015-06-30 Leo Lab Ltd Treatment of virally induces lesions
US20100189674A1 (en) 2007-05-11 2010-07-29 Sonneborn Inc. Petrolatum Having Silicone-Like Properties
US9388124B2 (en) 2010-12-22 2016-07-12 Leo Laboratories Limited Ingenol-3-acylates I
NZ612446A (en) * 2010-12-22 2015-09-25 Leo Lab Ltd Ingenol-3-acylates iii and ingenol-3-carbamates
WO2012083954A1 (en) 2010-12-22 2012-06-28 Leo Pharma A/S 3-acyl-ingenols ii

Also Published As

Publication number Publication date
MX2014015497A (es) 2015-03-06
WO2014001215A2 (en) 2014-01-03
ZA201409022B (en) 2016-03-30
CN104411685A (zh) 2015-03-11
CN104411685B (zh) 2017-03-29
US9422309B2 (en) 2016-08-23
MY169215A (en) 2019-03-18
DK2864290T3 (en) 2017-10-02
JP2015521639A (ja) 2015-07-30
EP2864290B1 (en) 2017-06-14
HK1207624A1 (en) 2016-02-05
SG11201408016XA (en) 2015-03-30
IL235925A0 (en) 2015-02-01
ES2640612T3 (es) 2017-11-03
NZ702835A (en) 2017-05-26
KR20150024928A (ko) 2015-03-09
PL2864290T3 (pl) 2017-11-30
BR112014032244A2 (pt) 2017-06-27
JP6216781B2 (ja) 2017-10-18
EP2864290A2 (en) 2015-04-29
US20150175622A1 (en) 2015-06-25
CA2875461A1 (en) 2014-01-03
AU2013283511B2 (en) 2017-10-26
IN2014DN11023A (ru) 2015-09-25
AU2013283511A1 (en) 2014-12-18
WO2014001215A3 (en) 2014-02-27
PT2864290T (pt) 2017-09-19

Similar Documents

Publication Publication Date Title
JP7181967B2 (ja) 一過性受容体電位ａ１イオンチャネルの阻害
CA2925257C (en) 5imidazoquinolines and pyrimidine derivatives as potent modulators of vegf-driven angiogenic processes
RU2015102095A (ru) 3-о-гетероарилингенол
ES2828503T3 (es) Bloqueadores de los canales de sodio, método de preparación de los mismos y uso de los mismos
PH12015501058B1 (en) Pyrimidine-2,4-diamine derivatives for treatment of cancer
EP3707126A1 (en) Ire1 small molecule inhibitors
RU2612251C2 (ru) Соединения диоксин- и оксазин[2,3-d]пиримидина в качестве ингибиторов фосфоинозитид-3-киназы и способы их применения
WO2014062774A1 (en) Pyrazolopyrimidine compounds for the treatment of cancer
JP2015505816A (ja) Ｎｅｄｄ８活性化酵素阻害剤および低メチル化剤の投与
WO2019020559A1 (en) COMBINATION COMPRISING PALBOCICLIB AND 6- (2,4-DICHLOROPHENYL) -5- [4 - [(3S) -1- (3-FLUOROPROPYL) PYRROLIDIN-3-YL] OXYPHENYL] -8,9-DIHYDRO ACID -7H-BENZO [7] ANNULENE-2-CARBOXYLIC AND ITS USE FOR THE TREATMENT OF CANCER
ES2824801T3 (es) Sal de compuesto heterocíclico sustituido con halógeno
JP2015521639A5 (ru)
JPWO2013002365A1 (ja) 止痒剤
US11110089B2 (en) Pyridazinones and their use in the treatment of cancer
WO2020232403A1 (en) Treatment of fibrosis with ire1 small molecule inhibitors
CA3082839A1 (en) Methods of inhibiting tumor metastasis
JP2023532996A (ja) Ｆａｂｐ４調節化合物の抗ウイルス的使用
AU2012203914C1 (en) 5imidazoquinolines and pyrimidine derivatives as potent modulators of VEGF-driven angiogenic processes
WO2023109540A1 (zh) 具有akt激酶抑制活性的杂环化合物及其制备方法和医药用途
CN115785186A (zh) 甾体化合物及其应用
CN115772202A (zh) 一种甾体化合物及其应用
TW202228674A (zh) 藉由併用ｅｐ４拮抗藥與免疫檢查點抑制物質而進行之癌症治療
RU2018106663A (ru) Лечение витилиго

Legal Events

Date Code Title Description
FA94 Acknowledgement of application withdrawn (non-payment of fees)

Effective date: 20181228