RU2014132837A - Конъюгаты антагонистов интегрина для нацеленной доставки к клеткам, экспрессирующим lfa-1 - Google Patents
Конъюгаты антагонистов интегрина для нацеленной доставки к клеткам, экспрессирующим lfa-1 Download PDFInfo
- Publication number
- RU2014132837A RU2014132837A RU2014132837A RU2014132837A RU2014132837A RU 2014132837 A RU2014132837 A RU 2014132837A RU 2014132837 A RU2014132837 A RU 2014132837A RU 2014132837 A RU2014132837 A RU 2014132837A RU 2014132837 A RU2014132837 A RU 2014132837A
- Authority
- RU
- Russia
- Prior art keywords
- ethoxy
- compound
- formula
- propionylamino
- compounds
- Prior art date
Links
- PMRPYMROKIJRER-UHFFFAOYSA-N CC(C)NC(CCN(C(C=C1)=O)C1=O)=O Chemical compound CC(C)NC(CCN(C(C=C1)=O)C1=O)=O PMRPYMROKIJRER-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/545—Heterocyclic compounds
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- 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
- C07C327/00—Thiocarboxylic acids
- C07C327/02—Monothiocarboxylic acids
- C07C327/04—Monothiocarboxylic acids having carbon atoms of thiocarboxyl groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C327/06—Monothiocarboxylic acids having carbon atoms of thiocarboxyl groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of an acyclic saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C381/00—Compounds containing carbon and sulfur and having functional groups not covered by groups C07C301/00 - C07C337/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with 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
- C07D207/36—Oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/70—Sulfur atoms
- C07D213/71—Sulfur atoms to which a second hetero atom is attached
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/02—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B11/00—Diaryl- or thriarylmethane dyes
- C09B11/04—Diaryl- or thriarylmethane dyes derived from triarylmethanes, i.e. central C-atom is substituted by amino, cyano, alkyl
- C09B11/10—Amino derivatives of triarylmethanes
- C09B11/22—Amino derivatives of triarylmethanes containing OH groups bound to an aryl nucleus and their ethers and esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/44—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members
- C07D207/444—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members having two doubly-bound oxygen atoms directly attached in positions 2 and 5
- C07D207/448—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members having two doubly-bound oxygen atoms directly attached in positions 2 and 5 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. maleimide
- C07D207/452—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members having two doubly-bound oxygen atoms directly attached in positions 2 and 5 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. maleimide with hydrocarbon radicals, substituted by hetero atoms, directly attached to the ring nitrogen atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Saccharide Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
1. Соединение формулы I:или его фармацевтически приемлемая соль или сложный эфир; где n равно 1-24, и гдеR1 выбран из группы, состоящей из следующих соединений:(1) соединения формулы:;(2) соединения формулы:; и(3) соединения формулы:где Q представляет собой Η или ОН;R2 выбран из группы, состоящей из следующих соединений:(1) соединения формулы:;(2) соединения формулы:;(3) соединения формулы:; и(4) соединения формулы:где R3 представляет собой конъюгированную группировку, и представляет собой либо атом серы, либо соединение формулы:к ПЭГ. к S2. Соединение по п. 1, где R1 представляет собой соединение формулы:.3. Соединение по п. 1, где R1 представляет собой соединение формулы:.4. Соединение по п. 1, где R1 представляет собой соединение формулы:,где Q представляет собой Η или ОН.5. Соединение по п. 4, где Q представляет собой Н.6. Соединение по п. 4, где Q представляет собой ОН.7. Соединение по п. 1, где R2 представляет собой соединение формулы:.8. Соединение по п. 1, где R2 представляет собой соединение формулы:.9. Соединение по п. 1, где R2 представляет собой соединение формулы:.10. Соединение по п. 1, где R2 представляет собой соединение формулы:,где R3 представляет собой одно- или двунитевой олигонуклеотид, и X представляет собой либо атом серы, либо соединение формулы:к ПЭГ. к S11. Соединение по п. 10, где X представляет собой атом серы.12. Соединение по любому из пп. 10 или 11, где R3 представляет собой молекулу миРНК.13. Соединение по любому из пп. 7-10, где R1 представляет собой соединение формулы:.14. Соединение по любому из пп. 7-10, где R1 представляет собой соединение формулы:.15. Соединение по любому из пп. 7-10, где R1 представляет собой соединение формулы:где Q представляет собой Η или ОН.16. Соединение по п. 1, выбранное из группы, состоящей из следующих соединений:(S)-3-{3-{2-[2-(2-{2-[3-(2,5-диоксо-2,5-дигидро-пиррол-1-ил)-проп
Claims (24)
1. Соединение формулы I:
или его фармацевтически приемлемая соль или сложный эфир; где n равно 1-24, и где
R1 выбран из группы, состоящей из следующих соединений:
(1) соединения формулы:
(2) соединения формулы:
(3) соединения формулы:
где Q представляет собой Η или ОН;
R2 выбран из группы, состоящей из следующих соединений:
(1) соединения формулы:
(2) соединения формулы:
(3) соединения формулы:
(4) соединения формулы:
где R3 представляет собой конъюгированную группировку, и представляет собой либо атом серы, либо соединение формулы:
5. Соединение по п. 4, где Q представляет собой Н.
6. Соединение по п. 4, где Q представляет собой ОН.
11. Соединение по п. 10, где X представляет собой атом серы.
12. Соединение по любому из пп. 10 или 11, где R3 представляет собой молекулу миРНК.
16. Соединение по п. 1, выбранное из группы, состоящей из следующих соединений:
(S)-3-{3-{2-[2-(2-{2-[3-(2,5-диоксо-2,5-дигидро-пиррол-1-ил)-пропиониламино]-этокси]-этокси}-этокси)-этокси]-пропиониламино}-2-({2-[3-(3-гидроксифенил)-пропиламино]-4,6-диметилпиримидин-5-карбонил}амино)пропионовой кислоты; и
(S)-3-{3-(2-{2-[2-(2-{2-[2-(2-{2-[3-(2,5-диоксо-2,5-дигидропиррол-1-ил)-пропиониламино]-этокси)-этокси]-этокси}-этокси)-этокси]-этокси}-этокси)-этокси]-пропиониламино}-2-({2-[3-(3-гидроксифенил)-пропиламино]-4,6-диметилпиримидин-5-карбонил}амино)пропионовой кислоты.
17. Соединение по п. 1, выбранное из группы, состоящей из следующих соединений:
(S)-3-{3-[2-(2-{2-[2-(2-{2-[2-(2-{2-[2-(2-{2-[3-(2,5-диоксо-2,5-дигидро-пиррол-1-ил)-пропиониламино]-этокси}-этокси)-этокси]-этокси}-этокси)-этокси]-этокси}-этокси)-этокси]-этокси}-этокси)-этокси]-пропиониламино}-2-({2-[3-(3-гидрокси-фенил)-пропиламино]-4,6-диметилпиримидин-5-карбонил}амино)пропионовой кислоты; и
(S)-3-{4-[4-(3-(2-{2-[2-(2-{2-[2-(2-{2-этокси)-этокси]-этокси}-этокси)-этокси]-этокси}-этокси)-этокси]-аминопропокси)-2,6-дихлорбензоиламино]-фенил}-2-[2-хлор-4-(3-гидроксибензилкарбамоил)-бензоиламино]-пропионовой кислоты-ПЭГ8.
18. Соединение по п. 1, выбранное из группы, состоящей из следующих соединений:
S)-2-[2-хлор-4-(3-гидроксибензилкарбамоил)-бензоиламино]-3-(4-{2,6-дихлор-4-[3-(3-{2-[2-(2-{2-[3-(2,5-диоксо-2,5-дигидро-пиррол-1-ил)-пропиониламино]-этокси}-этокси)-этокси]-этокси}-пропиониламино)-пропокси]-бензоиламино}-фенил)-пропионовой кислоты; и
S)-2-[2-хлор-4-(3-гидроксибензилкарбамоил)-бензоиламино]-3-(4-{2,6-дихлор-4-[3-(3-{2-[2-(2-{2-2-[2-(2-{2-2-[2-(2-{2-[3-(2,5-диоксо-2,5-дигидро-пиррол-1-ил)-пропиониламино]-этокси}-этокси)-этокси]-этокси}-этокси}-этокси)-этокси]-этокси}-пропиониламино)-пропокси]-бензоиламино}-фенил)-пропионовой кислоты.
19. Соединение по п. 1, выбранное из группы, состоящей из следующих соединений:
S)-2-[2-хлор-4-(3-гидрокси-бензилкарбамоил)-бензоиламино]-3-(4-{2,6-дихлор-4-[3-(3-{2-[2-(2-{2-2-[2-(2-{2-[3-(2,5-диоксо-2,5-дигидропиррол-1-ил)-пропиониламино]-этокси}-этокси)-этокси]-этокси]-этокси}-этокси)-этокси]-этокси}-пропиониламино)-пропокси]-бензоиламино}-фенил)-пропионовой кислоты; и
(S)-3-{[(3-{3-[3-(2-{2-[2-(2-{2-[2-(2-{2-[3-(2,5-диоксо-2,5-дигидро-пиррол-1-ил)-пропиониламино]-этокси}-этокси)-этокси]-этокси}-этокси)-этокси]-этокси}-этокси)-пропиониламино]-пропилокси}-фенил)-карбонил]-амино}-2-({2-[3-(3-гидроксифенил)-пропиламино]-4,6-диметилпиримидин-5-карбонил}-амино)-пропионовой кислоты.
20. Соединение по п. 1, выбранное из группы, состоящей из следующих соединений:
(S)-3-{[(3-{3-[3-(2-{2-[2-(2-{2-[2-(2-{2-[3-(2,5-диоксо-2,5-дигидропиррол-1-ил)-пропиониламино]-этокси}-этокси)-этокси]-этокси}-этокси)-этокси]-этокси}-этокси)-пропиониламино]-пропилокси}-5-гидроксифенил)-карбонил]-амино}-2-({2-[3-(3-гидроксифенил)-пропиламино]-4,6-диметилпиримидин-5-карбонил}-амино)-пропионовой кислоты; и
(S)-3-[({3-[3-(3-{2-[2-(2-{2-[3-(2,5-диоксо-2,5-дигидропиррол-1-ил)-пропиониламино]-этокси}-этокси)-этокси]-этокси}-пропиониламино)-пропилокси]-5-гидроксифенил}-карбонил)-амино]-2-({2-[3-(3-гидроксифенил)-пропиламино]-4,6-диметилпиримидин-5-карбонил}-амино)-пропионовой кислоты.
21. Фармацевтическая композиция, содержащая соединение по любому из пп. 1-20 и фармацевтически приемлемый носитель.
22. Способ лечения воспаления, рака или метаболического заболевания или состояния, включающий введение пациенту, нуждающемуся в этом, терапевтически эффективного количества соединения по любому из пп. 1-20.
23. Применение соединения по любому из пп. 1-20 для лечения или профилактики воспаления, рака или метаболического заболевания или состояния.
24. Применение соединения по любому из пп. 1-20 для получения лекарственного средства для лечения или профилактики воспаления, рака или метаболического заболевания или состояния.
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261591297P | 2012-01-27 | 2012-01-27 | |
US61/591,297 | 2012-01-27 | ||
US201261678673P | 2012-08-02 | 2012-08-02 | |
US61/678,673 | 2012-08-02 | ||
PCT/EP2013/051273 WO2013110679A1 (en) | 2012-01-27 | 2013-01-24 | Integrin antagonist conjugates for targeted delivery to cells expressing lfa-1 |
Publications (2)
Publication Number | Publication Date |
---|---|
RU2014132837A true RU2014132837A (ru) | 2016-03-20 |
RU2624732C2 RU2624732C2 (ru) | 2017-07-06 |
Family
ID=47605526
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
RU2014132837A RU2624732C2 (ru) | 2012-01-27 | 2013-01-24 | Конъюгаты антагонистов интегрина для нацеленной доставки к клеткам, экспрессирующим lfa-1 |
Country Status (12)
Country | Link |
---|---|
US (2) | US20130197059A1 (ru) |
EP (1) | EP2806897B1 (ru) |
JP (1) | JP6182542B2 (ru) |
KR (1) | KR20140121453A (ru) |
CN (1) | CN104185478B (ru) |
BR (1) | BR112014017517A2 (ru) |
CA (1) | CA2857127A1 (ru) |
DK (1) | DK2806897T3 (ru) |
HK (1) | HK1202425A1 (ru) |
MX (1) | MX2014008590A (ru) |
RU (1) | RU2624732C2 (ru) |
WO (1) | WO2013110679A1 (ru) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20140121453A (ko) * | 2012-01-27 | 2014-10-15 | 에프. 호프만-라 로슈 아게 | Lfa-1 발현 세포로의 표적화 전달을 위한 인테그린 안타고니스트 |
US9447035B2 (en) * | 2012-01-27 | 2016-09-20 | Hoffmann-La Roche Inc. | Integrin antagonist conjugates for targeted delivery to cells expressing VLA-4 |
CN111825622A (zh) * | 2020-07-10 | 2020-10-27 | 西华大学 | 一种氧化脱氢芳构化制备2-嘧啶酮衍生物的方法 |
CN115028828B (zh) * | 2022-07-19 | 2023-09-15 | 西安超磁纳米生物科技有限公司 | 一种可靶向肝细胞的聚乙二醇衍生物及其制备方法 |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2301377C (en) * | 1997-08-22 | 2009-10-06 | F. Hoffmann-La Roche Ag | N-aroylphenylalanine derivatives |
US6229011B1 (en) * | 1997-08-22 | 2001-05-08 | Hoffman-La Roche Inc. | N-aroylphenylalanine derivative VCAM-1 inhibitors |
EP1403247A1 (en) * | 1997-08-22 | 2004-03-31 | F.Hoffmann-La Roche Ag | N-Alkanoylphenylalanine derivatives |
US6331640B1 (en) * | 1998-10-13 | 2001-12-18 | Hoffmann-La Roche Inc. | Diaminopropionic acid derivatives |
US6515124B2 (en) | 2000-02-09 | 2003-02-04 | Hoffman-La Roche Inc. | Dehydroamino acids |
US6774116B2 (en) * | 2001-04-17 | 2004-08-10 | Cryolife, Inc. | Prodrugs via acylation with cinnamate |
CA2609053C (en) * | 2005-05-17 | 2017-04-25 | Sarcode Corporation | Compositions and methods for treatment of eye disorders |
ES2475065T3 (es) | 2008-10-09 | 2014-07-10 | Tekmira Pharmaceuticals Corporation | Aminol�pidos mejorados y métodos para la administración de ácidos nucleicos |
CN103476951B (zh) * | 2011-02-16 | 2017-07-28 | 海德威技术公司 | 用于可检测的标记的靶标定位锚定的方法和组合物 |
US20120270875A1 (en) * | 2011-03-16 | 2012-10-25 | Paul Gillespie | Pyrimidine amide compounds |
CN104144706B (zh) * | 2012-01-27 | 2017-03-29 | 弗·哈夫曼-拉罗切有限公司 | 靶向递送至表达α‑V‑β‑3的细胞的整联蛋白拮抗剂结合物 |
KR20140121453A (ko) * | 2012-01-27 | 2014-10-15 | 에프. 호프만-라 로슈 아게 | Lfa-1 발현 세포로의 표적화 전달을 위한 인테그린 안타고니스트 |
-
2013
- 2013-01-24 KR KR1020147023815A patent/KR20140121453A/ko not_active Application Discontinuation
- 2013-01-24 DK DK13701434.6T patent/DK2806897T3/en active
- 2013-01-24 RU RU2014132837A patent/RU2624732C2/ru not_active IP Right Cessation
- 2013-01-24 WO PCT/EP2013/051273 patent/WO2013110679A1/en active Application Filing
- 2013-01-24 MX MX2014008590A patent/MX2014008590A/es unknown
- 2013-01-24 CN CN201380006132.9A patent/CN104185478B/zh active Active
- 2013-01-24 CA CA2857127A patent/CA2857127A1/en not_active Abandoned
- 2013-01-24 EP EP13701434.6A patent/EP2806897B1/en active Active
- 2013-01-24 US US13/748,648 patent/US20130197059A1/en not_active Abandoned
- 2013-01-24 BR BR112014017517A patent/BR112014017517A2/pt unknown
- 2013-01-24 US US14/373,989 patent/US9650363B2/en active Active
- 2013-01-24 JP JP2014553706A patent/JP6182542B2/ja not_active Expired - Fee Related
-
2015
- 2015-03-23 HK HK15102939.3A patent/HK1202425A1/xx unknown
Also Published As
Publication number | Publication date |
---|---|
CN104185478A (zh) | 2014-12-03 |
DK2806897T3 (en) | 2017-10-16 |
BR112014017517A2 (pt) | 2017-06-13 |
KR20140121453A (ko) | 2014-10-15 |
MX2014008590A (es) | 2015-03-03 |
JP2015508055A (ja) | 2015-03-16 |
WO2013110679A1 (en) | 2013-08-01 |
US20150065534A1 (en) | 2015-03-05 |
CN104185478B (zh) | 2016-10-12 |
HK1202425A1 (en) | 2015-10-02 |
US9650363B2 (en) | 2017-05-16 |
RU2624732C2 (ru) | 2017-07-06 |
CA2857127A1 (en) | 2013-08-01 |
JP6182542B2 (ja) | 2017-08-16 |
EP2806897A1 (en) | 2014-12-03 |
US20130197059A1 (en) | 2013-08-01 |
EP2806897B1 (en) | 2017-08-02 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
RU2014132565A (ru) | Конъюгаты антагонистов интегрина для нацеленной доставки к клеткам, экспрессирующийм альфа-v-бета-3 | |
JP6833811B2 (ja) | 荷電イオンチャネル遮断薬及び使用方法 | |
NZ593030A (en) | Pyridyloxyindoles inhibitors of vegf-r2 and use thereof for treatment of disease | |
RU2014132837A (ru) | Конъюгаты антагонистов интегрина для нацеленной доставки к клеткам, экспрессирующим lfa-1 | |
JP2012520342A5 (ru) | ||
RU2014132564A (ru) | Хитозан, ковалентно связанный с низкомолекулярным антагонистом интегрина, для нацеленной доставки | |
JP2012517470A5 (ru) | ||
RU2008129723A (ru) | Ингибиторы ccr9 активности | |
RU2017127135A (ru) | Терапевтическое средство против рака желчных протоков | |
NZ599136A (en) | Substituted carbamoylmethylamino acetic acid derivatives as novel nep inhibitors | |
RU2600440C3 (ru) | Твердые композиции, содержащие агонист glp-1 и соль n-(8-(2-гидроксибензоил)амино)каприловой кислоты | |
RU2009111273A (ru) | 5-замещенные изоиндолиновые соединения | |
UA107578C2 (uk) | Комбінована терапія при лікуванні діабету | |
EA200801165A1 (ru) | Антагонисты неосновного рецептора-1 меланинконцентрирующего гормона | |
PH12012500765A1 (en) | Boronic acids and esters as inhibitors of fatty acid amide hydrolase | |
MX2010002675A (es) | Profarmacos para analogos de hormonas tiroideas. | |
MX2010005342A (es) | Compuestos indola y metodos para tratar el dolor visceral. | |
RU2013155586A (ru) | [1,3]оксазины | |
RU2014112108A (ru) | Составы с производными децитабина | |
JP2013532668A5 (ru) | ||
JP2014502979A5 (ru) | ||
PE20080360A1 (es) | Derivados 4-bencilftalazinona 2-sustituidos como antagonistas de histaminas h1 y h3 | |
BR112014011981A2 (pt) | formulações farmacêuticas | |
JP2011520836A5 (ru) | ||
RU2013148146A (ru) | Производные адамантила |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM4A | The patent is invalid due to non-payment of fees |
Effective date: 20190125 |