HRP20140218T4 - Polimerni konjugati k-252a i njihovi derivati - Google Patents
Polimerni konjugati k-252a i njihovi derivati Download PDFInfo
- Publication number
- HRP20140218T4 HRP20140218T4 HRP20140218TT HRP20140218T HRP20140218T4 HR P20140218 T4 HRP20140218 T4 HR P20140218T4 HR P20140218T T HRP20140218T T HR P20140218TT HR P20140218 T HRP20140218 T HR P20140218T HR P20140218 T4 HRP20140218 T4 HR P20140218T4
- Authority
- HR
- Croatia
- Prior art keywords
- substituted
- unsubstituted
- polymer
- group
- hydrogen
- Prior art date
Links
- 229920000642 polymer Polymers 0.000 title claims 46
- 229910052739 hydrogen Inorganic materials 0.000 claims 21
- 239000001257 hydrogen Substances 0.000 claims 21
- 125000000217 alkyl group Chemical group 0.000 claims 20
- 150000002431 hydrogen Chemical group 0.000 claims 15
- 125000003342 alkenyl group Chemical group 0.000 claims 13
- 125000000304 alkynyl group Chemical group 0.000 claims 13
- 239000003814 drug Substances 0.000 claims 11
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 10
- 125000003545 alkoxy group Chemical group 0.000 claims 8
- 230000007170 pathology Effects 0.000 claims 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 7
- 125000004122 cyclic group Chemical group 0.000 claims 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 6
- 125000003118 aryl group Chemical group 0.000 claims 6
- 229940079593 drug Drugs 0.000 claims 6
- 125000001072 heteroaryl group Chemical group 0.000 claims 6
- 230000002265 prevention Effects 0.000 claims 6
- 239000002202 Polyethylene glycol Substances 0.000 claims 5
- 125000002252 acyl group Chemical group 0.000 claims 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 5
- 230000000116 mitigating effect Effects 0.000 claims 5
- -1 nitro, carbamoyl Chemical group 0.000 claims 5
- 229920001223 polyethylene glycol Polymers 0.000 claims 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 4
- 239000002253 acid Substances 0.000 claims 4
- 150000001875 compounds Chemical class 0.000 claims 4
- 201000010099 disease Diseases 0.000 claims 4
- 230000002500 effect on skin Effects 0.000 claims 4
- 125000000524 functional group Chemical group 0.000 claims 4
- 229910052736 halogen Inorganic materials 0.000 claims 4
- 150000002367 halogens Chemical class 0.000 claims 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 4
- 229910052757 nitrogen Inorganic materials 0.000 claims 4
- 239000000126 substance Substances 0.000 claims 4
- 101100339431 Arabidopsis thaliana HMGB2 gene Proteins 0.000 claims 3
- 102000055207 HMGB1 Human genes 0.000 claims 3
- 108700010013 HMGB1 Proteins 0.000 claims 3
- 101150021904 HMGB1 gene Proteins 0.000 claims 3
- 239000013543 active substance Substances 0.000 claims 3
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims 3
- 239000008177 pharmaceutical agent Substances 0.000 claims 3
- 208000023275 Autoimmune disease Diseases 0.000 claims 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims 2
- 229920001661 Chitosan Polymers 0.000 claims 2
- 208000035473 Communicable disease Diseases 0.000 claims 2
- 229920002307 Dextran Polymers 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 208000012902 Nervous system disease Diseases 0.000 claims 2
- 208000025966 Neurological disease Diseases 0.000 claims 2
- 208000031481 Pathologic Constriction Diseases 0.000 claims 2
- 229920002845 Poly(methacrylic acid) Polymers 0.000 claims 2
- 229920000954 Polyglycolide Polymers 0.000 claims 2
- 201000004681 Psoriasis Diseases 0.000 claims 2
- 229920002125 Sokalan® Polymers 0.000 claims 2
- 150000001412 amines Chemical class 0.000 claims 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 2
- PJVZQNVOUCOJGE-CALCHBBNSA-N chembl289853 Chemical compound N1([C@H]2CC[C@H](O2)N2[C]3C=CC=CC3=C3C2=C11)C2=CC=C[CH]C2=C1C1=C3C(=O)N(C)C1=O PJVZQNVOUCOJGE-CALCHBBNSA-N 0.000 claims 2
- 230000021615 conjugation Effects 0.000 claims 2
- 125000005842 heteroatom Chemical group 0.000 claims 2
- 125000000623 heterocyclic group Chemical group 0.000 claims 2
- 229920001427 mPEG Polymers 0.000 claims 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 2
- 229920000233 poly(alkylene oxides) Polymers 0.000 claims 2
- 229920000747 poly(lactic acid) Polymers 0.000 claims 2
- 229920002401 polyacrylamide Polymers 0.000 claims 2
- 229920000058 polyacrylate Polymers 0.000 claims 2
- 239000004584 polyacrylic acid Substances 0.000 claims 2
- 229920001515 polyalkylene glycol Polymers 0.000 claims 2
- 229920000120 polyethyl acrylate Polymers 0.000 claims 2
- 239000004633 polyglycolic acid Substances 0.000 claims 2
- 239000004626 polylactic acid Substances 0.000 claims 2
- 229920000193 polymethacrylate Polymers 0.000 claims 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
- 208000037803 restenosis Diseases 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- 230000036262 stenosis Effects 0.000 claims 2
- 208000037804 stenosis Diseases 0.000 claims 2
- 230000000699 topical effect Effects 0.000 claims 2
- 208000002874 Acne Vulgaris Diseases 0.000 claims 1
- 201000001320 Atherosclerosis Diseases 0.000 claims 1
- 208000012657 Atopic disease Diseases 0.000 claims 1
- 208000009137 Behcet syndrome Diseases 0.000 claims 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 1
- 206010006895 Cachexia Diseases 0.000 claims 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 208000032544 Cicatrix Diseases 0.000 claims 1
- 208000027205 Congenital disease Diseases 0.000 claims 1
- 201000004624 Dermatitis Diseases 0.000 claims 1
- 206010012438 Dermatitis atopic Diseases 0.000 claims 1
- 208000004454 Hyperalgesia Diseases 0.000 claims 1
- 208000035154 Hyperesthesia Diseases 0.000 claims 1
- 208000002260 Keloid Diseases 0.000 claims 1
- 208000004852 Lung Injury Diseases 0.000 claims 1
- 206010029098 Neoplasm skin Diseases 0.000 claims 1
- 206010063837 Reperfusion injury Diseases 0.000 claims 1
- 208000017442 Retinal disease Diseases 0.000 claims 1
- 206010038923 Retinopathy Diseases 0.000 claims 1
- 206010040047 Sepsis Diseases 0.000 claims 1
- 208000021386 Sjogren Syndrome Diseases 0.000 claims 1
- 208000000453 Skin Neoplasms Diseases 0.000 claims 1
- 206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 claims 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 1
- 206010052779 Transplant rejections Diseases 0.000 claims 1
- 206010069363 Traumatic lung injury Diseases 0.000 claims 1
- 206010046851 Uveitis Diseases 0.000 claims 1
- 206010047115 Vasculitis Diseases 0.000 claims 1
- 206010000496 acne Diseases 0.000 claims 1
- 230000001154 acute effect Effects 0.000 claims 1
- 125000004423 acyloxy group Chemical group 0.000 claims 1
- 239000000654 additive Substances 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 125000003282 alkyl amino group Chemical group 0.000 claims 1
- 125000005103 alkyl silyl group Chemical group 0.000 claims 1
- 208000026935 allergic disease Diseases 0.000 claims 1
- 230000000172 allergic effect Effects 0.000 claims 1
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims 1
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 201000008937 atopic dermatitis Diseases 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 210000003169 central nervous system Anatomy 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000002526 effect on cardiovascular system Effects 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
- 230000001969 hypertrophic effect Effects 0.000 claims 1
- 230000000642 iatrogenic effect Effects 0.000 claims 1
- 208000036260 idiopathic disease Diseases 0.000 claims 1
- FQKSBRCHLNOAGY-UHFFFAOYSA-N indolo[2,3-a]carbazole Chemical group C1=CC=C2N=C3C4=NC5=CC=CC=C5C4=CC=C3C2=C1 FQKSBRCHLNOAGY-UHFFFAOYSA-N 0.000 claims 1
- 208000027866 inflammatory disease Diseases 0.000 claims 1
- 230000002757 inflammatory effect Effects 0.000 claims 1
- 230000035987 intoxication Effects 0.000 claims 1
- 231100000566 intoxication Toxicity 0.000 claims 1
- 210000001117 keloid Anatomy 0.000 claims 1
- 210000002510 keratinocyte Anatomy 0.000 claims 1
- 208000017169 kidney disease Diseases 0.000 claims 1
- 125000005647 linker group Chemical group 0.000 claims 1
- 239000002502 liposome Substances 0.000 claims 1
- 239000007788 liquid Substances 0.000 claims 1
- 231100000515 lung injury Toxicity 0.000 claims 1
- 206010025135 lupus erythematosus Diseases 0.000 claims 1
- 208000030159 metabolic disease Diseases 0.000 claims 1
- 230000002503 metabolic effect Effects 0.000 claims 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 1
- 201000006417 multiple sclerosis Diseases 0.000 claims 1
- 210000000653 nervous system Anatomy 0.000 claims 1
- 230000004770 neurodegeneration Effects 0.000 claims 1
- 230000007823 neuropathy Effects 0.000 claims 1
- 201000001119 neuropathy Diseases 0.000 claims 1
- 210000000056 organ Anatomy 0.000 claims 1
- 125000003544 oxime group Chemical group 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- 230000002093 peripheral effect Effects 0.000 claims 1
- 210000001428 peripheral nervous system Anatomy 0.000 claims 1
- 206010035116 pityriasis rubra pilaris Diseases 0.000 claims 1
- 150000003254 radicals Chemical class 0.000 claims 1
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 1
- 231100000241 scar Toxicity 0.000 claims 1
- 230000037387 scars Effects 0.000 claims 1
- 239000007787 solid Substances 0.000 claims 1
- 238000007910 systemic administration Methods 0.000 claims 1
- 230000009885 systemic effect Effects 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 238000002054 transplantation Methods 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
- C08G73/06—Polycondensates having nitrogen-containing heterocyclic rings in the main chain of the macromolecule
- C08G73/0666—Polycondensates containing five-membered rings, condensed with other rings, with nitrogen atoms as the only ring hetero atoms
- C08G73/0672—Polycondensates containing five-membered rings, condensed with other rings, with nitrogen atoms as the only ring hetero atoms with only one nitrogen atom in the ring
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G61/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
- C08G61/12—Macromolecular compounds containing atoms other than carbon in the main chain of the macromolecule
-
- 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
- A61K31/74—Synthetic polymeric materials
- A61K31/765—Polymers containing oxygen
-
- 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
- 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
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G61/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
- C08G61/12—Macromolecular compounds containing atoms other than carbon in the main chain of the macromolecule
- C08G61/122—Macromolecular compounds containing atoms other than carbon in the main chain of the macromolecule derived from five- or six-membered heterocyclic compounds, other than imides
- C08G61/123—Macromolecular compounds containing atoms other than carbon in the main chain of the macromolecule derived from five- or six-membered heterocyclic compounds, other than imides derived from five-membered heterocyclic compounds
- C08G61/124—Macromolecular compounds containing atoms other than carbon in the main chain of the macromolecule derived from five- or six-membered heterocyclic compounds, other than imides derived from five-membered heterocyclic compounds with a five-membered ring containing one nitrogen atom in the ring
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Polymers & Plastics (AREA)
- Dermatology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Communicable Diseases (AREA)
- Immunology (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Oncology (AREA)
- Physical Education & Sports Medicine (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
- Polyethers (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Claims (33)
1. Polimerni konjugat spoja indolokarbazola opće formule (I):
[image]
gdje su Ra i Rb nezavisno vodik ili organski ostatak izabran iz grupe koju čine supstituirani ili nesupstituirani niži alkil, supstituirani ili nesupstituirani niži alkenil, supstituirani ili nesupstituirani niži alkinil, hidroksi, niži alkoksi, karboksi ili alkoksikarbonil; ili
Ra i Rb zajedno formiraju 5-7 –članu cikličnu strukturu fuzioniranu direktno za strukturu jezgre indolo[2,3-a]karbazola, koja sadrži 0, 1 ili 2 heteroatoma i koja izborno sadrži karbonil grupu i cikličnu strukturu koja je nesupstituirana ili supstituirana sa najmanje jednom supstituirajućom grupom izabranom od karbonil grupe ili W1 ili W2 i pri čemu ako je heteroatom član ciklične strukture dušik, dušik je supstituiran sa ostatkom R3; i
gdje, Rc i Rd su
(a) nezavisno vodik ili organski ostatak izabran iz grupe koju čine supstituirani ili nesupstituirani niži alkil, supstituirani ili nesupstituirani niži alkenil, supstituirani ili nesupstituirani niži alkinil, hidroksi, niži alkoksi, karboksi ili alkoksikarbonil; ili
jedan od Rc i Rd je izabran od vodika, supstituiranog ili nesupstituiranog nižeg alkila i hidroksi, dok, drugi od Rc i Rd je 3-7 –člana ciklična grupa, pri čemu je ciklična grupa nesupstituirana ili supstituirana, sa najmanje jednom funkcionalnom grupom pogodnom za konjugaciju polimerne grupe, ili
(b) Rc i Rd zajedno formiraju 3-7 –članu cikličnu grupu, pri čemu je ciklična grupa nesupstituirana ili supstituirana sa najmanje jednom funkcinalnom grupom pogodnom za konjugaciju polimerne grupe, i
pri čemu su R1 i R2 isti ili različiti ostatak i svaki je nezavisno izabran iz grupe koju čine:
(a) vodik, halogen, supstituirani ili nesupstituirani niži alkil, supstituirani ili nesupstituirani niži alkenil, supstituirani ili nesupstituirani niži alkinil, hidroksi, niži alkoksi, karboksi, niži alkoksikarbonil, acil, nitro, karbamoil, niži alkilaminokarbonil, -NR5R6, gdje su svaki R5 i R6 nezavisno izabrani od vodika, supstituiranog ili nesupstituiranog nižeg alkila, supstituiranog ili nesupstituiranog nižeg alkenila, supstituiranog ili nesupstituiranog nižeg alkinila, supstituiranog ili nesupstituiranog arila, supstituiranog ili nesupstituiranog heteroarila, supstituiranog ili nesupstituiranog aralkila, supstituiranog ili nesupstituiranog nižeg alkilaminokarbonila, supstituiranog ili nesupstituiranog nižeg arilaminokarbonila, alkoksikarbonila, karbamoila, acila ili R5 i R6 su spojeni sa atomom dušika iz heterociklične grupe,
(b) -CO(CH2)jR4, gdje je j jednako 1 do 6, i R4 je izabran iz grupe koju čine
(i) vodik, halogen, -N3,
(ii) -NR5R6, gdje su R5 i R6 kao što su definirani u prethodnom tekstu,
(iii) -SR7, gdje je R7 izabran iz grupe koju čine vodik, supstituirani ili nesupstituirani niži alkil, supstituirani ili nesupstituirani niži alkenil, supstituirani ili nesupstituirani niži alkinil, supstituirani ili nesupstituirani aril, supstituirani ili nesupstituirani heteroaril, supstituirani ili nesupstituirani aralkil, -(CH2)aCO2R10 (gdje je a jednako 1 ili 2, i gdje je R10 izabran iz grupe koju čine vodik i supstituirani ili nesupstituirani niži alkil) i -(CH2)aCO2NR5R6,
(iv) -OR8, -OCOR8, gdje je R8 izabran od vodika, supstituiranog ili nesupstituiranog nižeg alkila, supstituiranog ili nesupstituiranog nižeg alkenila, supstituiranog ili nesupstituiranog nižeg alkinila, supstituiranog ili nesupstituiranog arila, supstituiranog ili nesupstituiranog heteroarila
(c) -CH(OH)(CH2)j R4, gdje su j i R4 kao što su definirani u prethodnom tekstu;
(d) -(CH2)dCHR11CO2R12 ili -(CH2)dCHR11CONR5R6, gdje je d jednako 0 do 5, R11 je vodik, -CONR5R6, ili -CO2R13, gdje, R13 je vodik ili supstituirani ili nesupstituirani niži alkil, i R12 je vodik ili supstituirani ili nesupstituirani niži alkil;
(e) -(CH2)kR14 gdje, k je 2 do 6 i R14 je halogen, supstituirani ili nesupstituirani aril, supstituirani ili nesupstituirani heteroaril, -COOR15, -OR15, (gdje, R15 je vodik, supstituirani ili nesupstituirani niži alkil, supstituirani ili nesupstituirani niži alkenil, supstituirani ili nesupstituirani niži alkinil, supstituirani ili nesupstituirani aril, supstituirani ili nesupstituirani heteroaril ili acil), -SR7 (gdje je R7 kao što je definiran u prethodnom tekstu), -CONR5R6, -NR5R8(gdje su R5 i R6 kao što su definirani u prethodnom tekstu) ili -N3;
(f) -CH=CH(CH2)mR16, gdje je m jednako 0 do 4, i R16 je vodik, supstituirani ili nesupstituirani niži alkil, supstituirani ili nesupstituirani niži alkenil, supstituirani ili nesupstituirani niži alkinil, supstituirani ili nesupstituirani aril, supstituirani ili nesupstituirani heteroaril, -COOR15, -OR15 (gdje je R15 kao što je definiran u prethodnom tekstu) -CONR5R6 ili -NR5R6 (gdje su R5 i R6 kao što su definirani u prethodnom tekstu);
(g) -CH=C(CO2R12)2, gdje je R12 kao što je definiran u prethodnom tekstu;
(h) -C≡C(CH2)nR16, gdje je n jednako 0 do 4 i R16 je kao što je definiran u prethodnom tekstu;
(i) -CH2OR22, gdje, R22 je tri-niži alkil silil u kojem su tri niže alkil grupe iste ili različite ili gdje R22 ima isto značenje kao R8.
(j) -CH(SR23)2 i -CH2-SR7 gdje, R23 je niži alkil, niži alkenil ili niži alkinil i gdje R7 je kao što je definiran u prethodnom tekstu; i
R3 je vodik, halogen, acil, karbamoil, supstituirani ili nesupstituirani niži alkil, supstituirani ili nesupstituirani alkenil, supstituirani ili nesupstituirani niži alkinil ili amino; i
W1 i W2 su nezavisno vodik, hidroksi ili W1 i W2 zajedno predstavljaju kisik;
ili njegova farmaceutski prihvatljiva sol,
naznačen time što spoj formule (I) ima najmanje jednu funkcionalnu grupu za koju je konjugirana polimerna grupa,
pri čemu je najmanje jedna funkcionlna grupa za koju je polimerna grupa konjugirana izabrana od hidroksi, supstituiranog ili nesupstituiranog nižeg alkila, nižeg alkoksi, karboksi, alkoksikarbonil, amino, nižeg alkilamino, nižeg alkilaminokarbonila i/ili oksim grupe i
pri čemu polimer je polimer izabran od polialkilen glikola, polialkilen oksida, poliakrilne kiseline, poliakrilata, poliakrilamida ili njihovih N-alkil derivata, polimetakrilne kiseline, polimetakrilata, polietilakrilne kiseline, polietilakrilata, polivinilpirolidona, poli(vinilalkohola), poliglikolne kiseline, polimliječne kiseline, poli (mliječne-ko-glikolne) kiseline, dektrana ili hitosana, i
pri čemu termin "niži alkil" kada se koristi pojedinačno ili u kombinaciji sa drugim grupama označava ravnolančanu ili razgranatu nižu alkil grupu koja sadrži od 1-6 atoma ugljika,
termin "niži alkenil" označava C2-C6 alkenil grupu koja može biti ravnolančana ili razgranata i može biti u Z ili E obliku,
termin "niži alkinil" označava C2-C6-alkinil grupu koja može biti ravnolančana ili razgranata, i
termin "niži alkoksi" označava alkoksi grupu koja sadrži od 1 do 6 atoma ugljika.
2. Polimerni konjugat prema patentnom zahtjevu 1, naznačen time što, spoj indolokarbazola formule (I) je spoj opće formule (II):
[image]
3. Polimerni konjugat prema patentnom zahtjevu 1 ili 2 predstavljen slijedećom formulom (III):
[image]
pri čemu su R1, R2, R3 i W1 i W2 kao što su definirani u patentnom zahtjevu 1; i pri čemu X predstavlja -L1-X’ i Y predstavlja -L2-Y’, pri čemu je najmanje jedan od X’ i Y’ polimer, bilo linearni ili razgranati, koji je vezan preko L1 i/ili L2 za prsten tetrahidrofurana spoja formule (III); L1 i/ili L2 su kovalentna kemijska veza ili linker grupa;
kada je Y’ polimer i X’ nije polimer, L1 je kovalentna kemijska veza i X’ je izabran iz grupe koju čine
(a) vodik, niži hidroksialkil, acil, karboksi, niži alkoksikarbonil,
(b) -CONR17aR17b, pri čemu su svaki R17a i R17b nezavisno izabrani od
(i) vodika, nižeg alkila, nižeg alkenila, nižeg alkinila,
(ii) -CH2 R18; pri čemu je R18 jednako hidroksi, ili
(iii) -NR19R20, pri čemu su svaki R19 ili R20 nezavisno izabrani od vodika, nižeg alkila, nižeg alkenila, nižeg alkinila ili R19 ili R20 su nezavisno ostatak α-aminokiseline i kome je hidroksi grupa karboksil grupe isključena, ili R19 ili R20 su spojeni sa atomom dušika tako da formiraju heterocikličnu grupu; i
(c) -CH=N-R21, pri čemu, R21 je hidroksi, niži alkoksi, amino, guanidino ili imidazolilamino;
kada je X’ polimer i Y’ nije polimer, L2 je kovalentna kemijska veza i Y’ je izabran od hidroksi, nižeg alkoksi, aralkiloksi ili aciloksi;
i pri čemu polimer je polimer izabran od polialkilen glikola, polialkilen oksida, poliakrilne kiseline, poliakrilata, poliakrilamida ili njihovih N-alkil derivata, polimetakrilne kiseline, polimetakrilata, polietilakrilne kiseline, polietilakrilata, polivinilpirolidona, poli(vinilalkohola), poliglikolne kiseline, polimliječne kiseline, poli (mliječne-ko-glikolne) kiseline, dektrana ili hitosana,
ili njegova farmaceutski prihvatljiva sol.
4. Polimerni konjugat prema bilo kojem od patentnih zahtjeva 1 do 3, naznačen time što, polimer je polimer izabran od polietilen glikola (PEG) ili metoksi-polietilen glikola (m-PEG).
5. Polimerni konjugat prema bilo kojem od patentnih zahtjeva 1 do 4, naznačen time što, polimer je polimer koji ima molekularnu težinu od 100 do 100 000 Da.
6. Polimerni konjugat prema patentnom zahtjevu 4 ili 5, naznačen time što, polimer je PEG ili mPEG sa prosječnom molekularnom težinom od 2 000 Da ili 5 000 Da.
7. Polimerni konjugat prema patentnom zahtjevu 4 ili 5, naznačen time što, polimer je PEG ili mPEG sa prosječnom molekularnom težinom od 550 Da ili 1100 Da.
8. Polimerni konjugat prema bilo kojem od patentnih zahtjeva od 2 do 7, naznačen time što je kovalentna kemijska veza između polimera i spoja formula (I) ili (II) ili pri čemu su L1 i/ili L2 formule (III) izabrani od veze karbamata, etera, estera, uglika, amida i/ili amina.
9. Polimerni konjugat prema bilo kojem od patentnih zahtjeva 2 do 8, naznačen time što, R1, R2, R3, W1, i W2 su vodik, Y’ je polimer i X’ je metoksikarbonil ili karboksil.
10. Polimerni konjugat prema patentnom zahtjevu 9, naznačen time što je L2 veza etera ili karbamata.
11. Polimerni konjugat prema bilo kojem od patentnih zahtjeva 2 do 8, naznačen time što, R1, R2, R3, W1, i W2 su vodik, X’ je polimer i Y’ je hidroksi.
12. Polimerni konjugat prema patentnom zahtjevu 11, naznačen time što, L1 je veza amina ili amida.
13. Polimerni konjugat prema bilo kojem od prethodnih patentnih zahtjeva za uporabu kao aktivno sredstvo u lijeku.
14. Polimerni konjugat prema patentnom zahtjevu 13 za uporabu kao aktivno sredstvo u topikalnom lijeku.
15. Polimerni konjugat prema patentnom zahtjevu 13 za uporabu kao aktivno sredstvo u lijeku za sustavno liječenje.
16. Farmaceutsko sredstvo koje sadrži najmanje jedan polimerni konjugat prema bilo kojem od prethodnih patentnih zahtjeva, izborno zajedno sa farmaceutski prihvatljivim nosačima, adjuvantima, razblaživačima i/ili aditivom.
17. Farmaceutsko sredstvo prema patentnom zahtjevu 16 za dijagnostičku primjenu.
18. Farmaceutsko sredstvo prema patentnom zahtjevu 16 za terapeutsku primjenu.
19. Uporaba polimernog konjugata prema bilo kojem od patentnih zahtjeva 1 do 12 za proizvodnju lijeka za prevenciju, ublažavanje i/ili liječenje patologija povezanih sa HMGB1.
20. Uporaba prema patentnom zahtjevu 19, naznačena time što su patologije povezane sa HMGB1 stenoza, restenoza, ateroskleroza, reumatoidni artritis, autoimune bolesti, tumori, infektivne bolesti, sepsa, akutna inflamatorna povreda pluća, lupus eritematodes, neurodegenerativne bolesti, bolesti središnjeg i perifernog živčanog sustava i multipla skleroza.
21. Uporaba prema patentnom zahtjevu 20, naznačena time što, patologija povezana sa HMGB1 je stenoza ili restenoza.
22. Uporaba prema patentnim zahtjevima 19 do 21, naznačena time što je polimerni konjugat reverzibilno imobiliziran na površini medicinskog uređaja.
23. Uporaba polimernog konjugata prema bilo kojem od patentnih zahtjeva 1 do 12 za proizvodnju lijeka za prevenciju, ublažavanje i/ili liječenje neuroloških poremećaja, neuropatija i neurodegenerativnih poremećaja središnjeg i perifernog živčanog sustava.
24. Uporaba polimernog konjugata prema bilo kojem od patentnih zahtjeva 1 do 12 za proizvodnju lijeka za prevenciju, ublažavanje i/ili liječenje dermalnih patologija.
25. Uporaba prema patentnom zahtjevu 24, gdje su dermalne patologije naznačene hiperproliferacijom keratinocita.
26. Uporaba prema patentnom zahtjevu 24 ili patentnom zahtjevu 25, naznačena time što, dermalne patologije su psorijaza, atopijski dermatitis, kronični ekcem, akne, pitirijazis rubra pilaris, keloidi, hipertrofirajući ožiljci i tumori kože.
27. Uporaba prema patentnom zahtjevu 26, naznačena time što, dermalna patologija je psorijaza.
28. Uporaba polimernog konjugata prema bilo kojem od patentnih zahtjeva 1 do 12 za proizvodnju lijeka za prevenciju, ublažavanje i/ili liječenje boli i hiperalgezije povezane sa NGF.
29. Uporaba prema bilo kojem od patentnih zahtjeva 24 do 28, naznačena time što je lijek pripremljen za topikalnu primjenu.
30. Uporaba prema patentnom zahtjevu 29, naznačena time što se primjena izvodi u obliku lipozoma.
31. Uporaba polimernog konjugata prema bilo kojem od patentnih zahtjeva 1 do 12 za proizvodnju lijeka za prevenciju, ublažavanje i/ili liječenje inflamatornih bolesti, autoimunih bolesti, sindroma sustavnog inflamatornog odgovora, reperfuzione povrede poslije transplantacije organa, kardiovaskularnih zahvaćenosti, akušerskih i ginekoloških bolesti, infektivnih bolesti, alergijskih i atopijskih bolesti, patologija solidnog i tekućeg tumora, bolesti odbacivanja transplanta, kongenitalnih bolesti, dermatoloških bolesti, neuroloških bolesti, kaheksije, renalnih bolesti, stanja jatrogene intoksikacije, metaboličkih i idiopatskih bolesti i oftalmoloških bolesti.
32. Uporaba polimernog konjugata prema bilo kojem od patentnih zahtjeva 1 do 12 za proizvodnju lijeka za prevenciju, ublažavanje i/ili liječenje Behcetove bolesti, Sjögrenovog sindroma, vaskulitisa, uveitisa, retinopatija..
33. Uporaba prema patentnim zahtjevima 28, 31 ili 30 naznačena time što je lijek za sustavnu primjenu.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US71089005P | 2005-08-25 | 2005-08-25 | |
| US72045405P | 2005-09-27 | 2005-09-27 | |
| US81146906P | 2006-06-07 | 2006-06-07 | |
| EP06777076.8A EP1919979B2 (en) | 2005-08-25 | 2006-08-25 | Polymer conjugates of k-252a and derivatives thereof |
| PCT/EP2006/008374 WO2007022999A1 (en) | 2005-08-25 | 2006-08-25 | Polymer conjugates of k-252a and derivatives thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HRP20140218T1 HRP20140218T1 (en) | 2014-04-11 |
| HRP20140218T4 true HRP20140218T4 (hr) | 2017-06-16 |
Family
ID=37075187
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20140218TT HRP20140218T4 (hr) | 2005-08-25 | 2014-03-10 | Polimerni konjugati k-252a i njihovi derivati |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US8673347B2 (hr) |
| EP (1) | EP1919979B2 (hr) |
| JP (1) | JP5366548B2 (hr) |
| KR (1) | KR101379693B1 (hr) |
| AU (1) | AU2006284096B2 (hr) |
| BR (1) | BRPI0615277A2 (hr) |
| CA (1) | CA2620032C (hr) |
| CY (1) | CY1114995T1 (hr) |
| DK (1) | DK1919979T4 (hr) |
| EA (1) | EA017318B1 (hr) |
| ES (1) | ES2444003T5 (hr) |
| HK (1) | HK1123563A1 (hr) |
| HR (1) | HRP20140218T4 (hr) |
| IL (1) | IL189187A (hr) |
| MX (1) | MX2008002524A (hr) |
| NZ (1) | NZ566160A (hr) |
| PL (1) | PL1919979T5 (hr) |
| PT (1) | PT1919979E (hr) |
| RS (1) | RS53195B2 (hr) |
| SI (1) | SI1919979T2 (hr) |
| WO (1) | WO2007022999A1 (hr) |
Families Citing this family (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010503630A (ja) | 2006-09-15 | 2010-02-04 | クレアビリス・セラピューティクス・エスピーエー | ＨＭＧＢ１のＢｏｘ−ＡおよびＨＭＧＢ１のＢｏｘ−Ａ変異体のポリマー複合体 |
| EP2350075B1 (en) | 2008-09-22 | 2014-03-05 | Array Biopharma, Inc. | Substituted imidazo[1,2b]pyridazine compounds as trk kinase inhibitors |
| HUE057625T2 (hu) | 2008-10-22 | 2022-05-28 | Array Biopharma Inc | TRK kináz inhibitor szubsztituált pirazolo[1,5-a]pirimidin vegyületek |
| CN102264398B (zh) | 2008-12-22 | 2013-12-18 | 克雷毕里斯股份有限公司 | 合成吲哚并咔唑化合物的聚合物缀合物 |
| AR077468A1 (es) | 2009-07-09 | 2011-08-31 | Array Biopharma Inc | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa |
| WO2011146336A1 (en) | 2010-05-20 | 2011-11-24 | Array Biopharma Inc. | Macrocyclic compounds as trk kinase inhibitors |
| WO2014177510A2 (en) * | 2013-05-03 | 2014-11-06 | Creabilis Sa | Polymer conjugates of indolocarbazole compounds in the treatment of pruritus |
| US9688769B2 (en) | 2013-10-22 | 2017-06-27 | Novimmune S.A. | Methods and compositions for diagnosis and treatment of disorders in patients with elevated levels of TLR4 ligands and other biomarkers |
| TWI746426B (zh) | 2014-11-16 | 2021-11-21 | 美商亞雷生物製藥股份有限公司 | (S)-N-(5-((R)-2-(2,5-二氟苯基)-吡咯啶-1-基)-吡唑并[1,5-a]嘧啶-3-基)-3-羥基吡咯啶-1-甲醯胺硫酸氫鹽結晶型 |
| EA201792679A1 (ru) | 2015-06-01 | 2018-06-29 | Локсо Онколоджи, Инк. | Способы диагностики и лечения злокачественной опухоли |
| HUE053067T2 (hu) | 2015-07-16 | 2021-06-28 | Array Biopharma Inc | Helyettesített pirazolo[1,5-A]piridin vegyületek, mint RET kináz inhibitorok |
| RU2744852C2 (ru) | 2015-10-26 | 2021-03-16 | Локсо Онколоджи, Инк. | Точечные мутации в устойчивых к ингибитору trk злокачественных опухолях и связанные с ними способы |
| WO2017176751A1 (en) | 2016-04-04 | 2017-10-12 | Loxo Oncology, Inc. | Liquid formulations of (s)-n-(5-((r)-2-(2,5-difluorophenyl)-pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide |
| US10045991B2 (en) | 2016-04-04 | 2018-08-14 | Loxo Oncology, Inc. | Methods of treating pediatric cancers |
| MA44612A (fr) | 2016-04-04 | 2019-02-13 | Loxo Oncology Inc | Méthodes de traitement de cancers pédiatriques |
| JP7443057B2 (ja) | 2016-05-18 | 2024-03-05 | ロクソ オンコロジー， インコーポレイテッド | （Ｓ）－Ｎ－（５－（（Ｒ）－２－（２，５－ジフルオロフェニル）ピロリジン－１－イル）－ピラゾロ［１，５－ａ］ピリミジン－３－イル）－３－ヒドロキシピロリジン－１－カルボキサミドの調製 |
| JOP20190077A1 (ar) | 2016-10-10 | 2019-04-09 | Array Biopharma Inc | مركبات بيرازولو [1، 5-a]بيريدين بها استبدال كمثبطات كيناز ret |
| TWI704148B (zh) | 2016-10-10 | 2020-09-11 | 美商亞雷生物製藥股份有限公司 | 作為ｒｅｔ激酶抑制劑之經取代吡唑并[1,5-a]吡啶化合物 |
| JOP20190092A1 (ar) | 2016-10-26 | 2019-04-25 | Array Biopharma Inc | عملية لتحضير مركبات بيرازولو[1، 5-a]بيريميدين وأملاح منها |
| WO2018136661A1 (en) | 2017-01-18 | 2018-07-26 | Andrews Steven W | SUBSTITUTED PYRAZOLO[1,5-a]PYRAZINE COMPOUNDS AS RET KINASE INHIBITORS |
| WO2018136663A1 (en) | 2017-01-18 | 2018-07-26 | Array Biopharma, Inc. | Ret inhibitors |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| WO2018175301A1 (en) | 2017-03-20 | 2018-09-27 | Sienna Biopharmaceuticals, Inc. | Polymer conjugate of montesanib with reduced exposure |
| WO2018175340A1 (en) | 2017-03-20 | 2018-09-27 | Sienna Biopharmaceuticals, Inc. | Reduced exposure conjugates modulating therapeutic targets |
| WO2018175302A1 (en) | 2017-03-20 | 2018-09-27 | Sienna Biopharmaceuticals, Inc. | Polymer conjugates targeting c-src with reduced exposure |
| WO2018175315A1 (en) | 2017-03-20 | 2018-09-27 | Sienna Biopharmaceuticals, Inc. | Polymer conjugates of staurosporine derivatives having reduced exposure |
| WO2018208369A1 (en) | 2017-05-10 | 2018-11-15 | Sienna Biopharmaceuticals, Inc. | Uses of polymer conjugates of indolocarbazole compounds with reduced exposure |
| TWI791053B (zh) | 2017-10-10 | 2023-02-01 | 美商亞雷生物製藥股份有限公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之結晶形式及其醫藥組合物 |
| TWI812649B (zh) | 2017-10-10 | 2023-08-21 | 美商絡速藥業公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之調配物 |
| US20190247398A1 (en) | 2017-10-26 | 2019-08-15 | Array Biopharma Inc. | Formulations of a macrocyclic trk kinase inhibitor |
| WO2019126270A1 (en) * | 2017-12-20 | 2019-06-27 | Sienna Biopharmaceuticals, Inc. | Formulations for dermal delivery of polymer conjugates of indolocarbazole compounds with reduced exposure |
| CA3087972C (en) | 2018-01-18 | 2023-01-10 | Array Biopharma Inc. | Substituted pyrazolyl[4,3-c]pyridinecompounds as ret kinase inhibitors |
| WO2019143977A1 (en) | 2018-01-18 | 2019-07-25 | Array Biopharma Inc. | Substituted pyrrolo[2,3-d]pyrimidines compounds as ret kinase inhibitors |
| WO2019143991A1 (en) | 2018-01-18 | 2019-07-25 | Array Biopharma Inc. | SUBSTITUTED PYRAZOLO[3,4-d]PYRIMIDINE COMPOUNDS AS RET KINASE INHIBITORS |
| WO2019143971A2 (en) * | 2018-01-18 | 2019-07-25 | Sienna Biopharmaceuticals, Inc. | Formulations for dermal delivery of polymer conjugates of indolocarbazole compounds with reduced exposure |
| JP7223502B6 (ja) * | 2018-02-22 | 2024-02-08 | 公益財団法人川崎市産業振興財団 | 医薬組成物 |
| EP3773725A1 (en) | 2018-03-29 | 2021-02-17 | Loxo Oncology Inc. | Treatment of trk-associated cancers |
| WO2020023387A1 (en) * | 2018-07-23 | 2020-01-30 | Sienna Biopharmaceuticals, Inc. | Uses of polymer conjugates of indolocarbazole compounds with reduced exposure |
| CA3224945A1 (en) | 2018-07-31 | 2020-02-06 | Loxo Oncology, Inc. | Spray-dried dispersions, formulations, and polymorphs of (s)-5-amino-3-(4-((5-fluoro-2-methoxybenzamido)methyl)phenyl)-1-(1,1,1-trifluoropropan-2-yl)-1h-pyrazole-4-carboxamide |
| JP2022500383A (ja) | 2018-09-10 | 2022-01-04 | アレイ バイオファーマ インコーポレイテッド | Ｒｅｔキナーゼ阻害剤としての縮合複素環式化合物 |
| US20220081438A1 (en) | 2018-12-19 | 2022-03-17 | Array Biopharma Inc. | Substituted pyrazolo[1,5-a]pyridine compounds as inhibitors of fgfr tyrosine kinases |
| EP3898615A1 (en) | 2018-12-19 | 2021-10-27 | Array Biopharma, Inc. | 7-((3,5-dimethoxyphenyl)amino)quinoxaline derivatives as fgfr inhibitors for treating cancer |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1988007045A1 (en) | 1987-03-09 | 1988-09-22 | Kyowa Hakko Kogyo Co., Ltd. | Derivatives of physiologically active substance k-252 |
| US5461146A (en) * | 1992-07-24 | 1995-10-24 | Cephalon, Inc. | Selected protein kinase inhibitors for the treatment of neurological disorders |
| AU2001261324A1 (en) | 2000-05-08 | 2001-11-20 | Psoriasis Research Institute | Psoriasis treatment |
| ITMI20010562A1 (it) | 2001-03-16 | 2002-09-16 | Marco E Bianchi | Inibitori o antagonisti della proteina hmg1 per il trattamento di disordini vascolari |
| DE60225271T2 (de) * | 2001-05-09 | 2009-03-05 | Discoverx, Inc., Fremont | Screening auf enzyminhibitoren |
| EP1653972A1 (en) | 2003-07-23 | 2006-05-10 | Creabilis Therapeutics s.r.l. | Topical use of tyrosine kinase inhibitors of microbial origin to prevent and treat skin disorders characterised by excessive cell proliferation |
| MX2007001155A (es) | 2004-07-29 | 2007-08-14 | Creabilis Therapeutics Spa | Uso de inhibidores de k-252a y de quinasa para la prevencion o el tratamiento de patologias asociadas con hmgb1. |
| PE20060608A1 (es) * | 2004-10-13 | 2006-08-22 | Wyeth Corp | Analogos de 17-hidroxiwortmanina como inhibidores de pi3k |
-
2006
- 2006-08-25 AU AU2006284096A patent/AU2006284096B2/en active Active
- 2006-08-25 DK DK06777076.8T patent/DK1919979T4/en active
- 2006-08-25 SI SI200631734A patent/SI1919979T2/sl unknown
- 2006-08-25 EP EP06777076.8A patent/EP1919979B2/en active Active
- 2006-08-25 BR BRPI0615277-5A patent/BRPI0615277A2/pt active Search and Examination
- 2006-08-25 PL PL06777076T patent/PL1919979T5/pl unknown
- 2006-08-25 JP JP2008527402A patent/JP5366548B2/ja not_active Expired - Fee Related
- 2006-08-25 CA CA2620032A patent/CA2620032C/en not_active Expired - Fee Related
- 2006-08-25 EA EA200800661A patent/EA017318B1/ru not_active IP Right Cessation
- 2006-08-25 US US12/064,461 patent/US8673347B2/en active Active
- 2006-08-25 ES ES06777076.8T patent/ES2444003T5/es active Active
- 2006-08-25 RS RS20140104A patent/RS53195B2/sr unknown
- 2006-08-25 MX MX2008002524A patent/MX2008002524A/es active IP Right Grant
- 2006-08-25 NZ NZ566160A patent/NZ566160A/en not_active IP Right Cessation
- 2006-08-25 PT PT67770768T patent/PT1919979E/pt unknown
- 2006-08-25 WO PCT/EP2006/008374 patent/WO2007022999A1/en active Application Filing
- 2006-08-25 KR KR1020087007112A patent/KR101379693B1/ko active IP Right Grant
-
2008
- 2008-02-03 IL IL189187A patent/IL189187A/en not_active IP Right Cessation
-
2009
- 2009-02-10 HK HK09101201.4A patent/HK1123563A1/xx active IP Right Revival
-
2014
- 2014-03-10 HR HRP20140218TT patent/HRP20140218T4/hr unknown
- 2014-03-24 CY CY20141100227T patent/CY1114995T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HRP20140218T4 (hr) | Polimerni konjugati k-252a i njihovi derivati | |
| JP2009506000A5 (hr) | ||
| HRP20140836T1 (hr) | Sinteza polimernih konjugata spojeva indolokarbazola | |
| ES2881395T3 (es) | Composiciones y métodos para inhibir la actividad de la arginasa | |
| CA2695297C (en) | Substituted cc-1065 analogs and their conjugates | |
| KR101660996B1 (ko) | 남용에 대한 낮은 잠재성을 갖는 페길화 오피오이드 | |
| JP2022087180A (ja) | シラノールベースの治療用ペイロード | |
| EP2435053B1 (en) | Polyal drug conjugates comprising variable rate-releasing linkers | |
| EP2906246B1 (en) | Vegf neutralizing prodrugs comprising ranibizumab for the treatment of ocular conditions characterized by ocular neovascularization | |
| US20130053405A1 (en) | Carrier linked paliperidone prodrugs | |
| HUE030846T2 (en) | Conjugates of CC-1065 analogues and bifunctional linkers | |
| TW201417833A (zh) | 含有非天然胺基酸之藥物輸送共軛物及使用方法 | |
| JP2010510329A (ja) | ７，８−飽和−４，５−エポキシ−モルフィナニウム類似体 | |
| EP2485712A1 (en) | Subcutaneous paliperidone composition | |
| KR20150086308A (ko) | 벤다무스틴 유도체 및 그의 사용 방법 | |
| JP7341152B2 (ja) | ポリマープロドラッグ、並びにその皮下及び／又は筋肉内投与 | |
| US20240139327A1 (en) | Prodrug compound, preparation method therefor and use thereof | |
| US20230101564A1 (en) | Polyethylene glycol conjugate drug, and preparation method therefor and use thereof | |
| JP2010504318A (ja) | ｐＨ標的化薬剤送達のための組成物及び方法 | |
| WO2019154120A1 (zh) | 细胞毒性剂及其偶联物、其制备方法及用途 | |
| US20240016946A1 (en) | Drug-loaded macromolecule and preparation method therefor | |
| KR20180101567A (ko) | 오피오이드 수용체 길항제 컨쥬게이트 및 그의 용도 | |
| JP6817956B2 (ja) | 新規なグルタミン酸誘導体とブロック共重合体を含有する組成物及びその用途 | |
| TW202206106A (zh) | 一類載藥的大分子及其製備方法 | |
| US20150225439A1 (en) | Dendrimer Scaffolds for Pharmaceutical Use |