HRP20230873T1 - Heterociklički imunomodulatori kao inhibitori kontrolne točke pdl1 - Google Patents
Heterociklički imunomodulatori kao inhibitori kontrolne točke pdl1 Download PDFInfo
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- HRP20230873T1 HRP20230873T1 HRP20230873TT HRP20230873T HRP20230873T1 HR P20230873 T1 HRP20230873 T1 HR P20230873T1 HR P20230873T T HRP20230873T T HR P20230873TT HR P20230873 T HRP20230873 T HR P20230873T HR P20230873 T1 HRP20230873 T1 HR P20230873T1
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- 6alkyl
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- 125000000623 heterocyclic group Chemical group 0.000 title claims 3
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 title claims 2
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 title claims 2
- 239000002955 immunomodulating agent Substances 0.000 title claims 2
- 229940121354 immunomodulator Drugs 0.000 title claims 2
- 101100463133 Caenorhabditis elegans pdl-1 gene Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 26
- 239000003112 inhibitor Substances 0.000 claims 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 7
- 150000003839 salts Chemical class 0.000 claims 7
- 125000003118 aryl group Chemical group 0.000 claims 6
- 125000001424 substituent group Chemical group 0.000 claims 6
- 229910052736 halogen Inorganic materials 0.000 claims 5
- 150000002367 halogens Chemical class 0.000 claims 5
- 125000001072 heteroaryl group Chemical group 0.000 claims 5
- 206010028980 Neoplasm Diseases 0.000 claims 4
- 125000000217 alkyl group Chemical group 0.000 claims 4
- 201000011510 cancer Diseases 0.000 claims 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims 4
- 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 claims 3
- 239000002246 antineoplastic agent Substances 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- 208000015181 infectious disease Diseases 0.000 claims 3
- 230000003612 virological effect Effects 0.000 claims 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 2
- 102000001714 Agammaglobulinaemia Tyrosine Kinase Human genes 0.000 claims 2
- 108010029445 Agammaglobulinaemia Tyrosine Kinase Proteins 0.000 claims 2
- 208000035473 Communicable disease Diseases 0.000 claims 2
- 108020004459 Small interfering RNA Proteins 0.000 claims 2
- 239000000427 antigen Substances 0.000 claims 2
- 102000036639 antigens Human genes 0.000 claims 2
- 108091007433 antigens Proteins 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 229940127089 cytotoxic agent Drugs 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 2
- 102000006639 indoleamine 2,3-dioxygenase Human genes 0.000 claims 2
- 108020004201 indoleamine 2,3-dioxygenase Proteins 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 230000002265 prevention Effects 0.000 claims 2
- 239000004055 small Interfering RNA Substances 0.000 claims 2
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 2
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- 229940080328 Arginase inhibitor Drugs 0.000 claims 1
- 102100031151 C-C chemokine receptor type 2 Human genes 0.000 claims 1
- 101710149815 C-C chemokine receptor type 2 Proteins 0.000 claims 1
- 229940045513 CTLA4 antagonist Drugs 0.000 claims 1
- 102000019034 Chemokines Human genes 0.000 claims 1
- 108010012236 Chemokines Proteins 0.000 claims 1
- 108020004638 Circular DNA Proteins 0.000 claims 1
- 229940122806 Cyclophilin inhibitor Drugs 0.000 claims 1
- 102000004127 Cytokines Human genes 0.000 claims 1
- 108090000695 Cytokines Proteins 0.000 claims 1
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 claims 1
- 229940127399 DNA Polymerase Inhibitors Drugs 0.000 claims 1
- 102100031780 Endonuclease Human genes 0.000 claims 1
- 108010042407 Endonucleases Proteins 0.000 claims 1
- -1 HBV entry inhibitor Substances 0.000 claims 1
- 229940122800 HBV entry inhibitor Drugs 0.000 claims 1
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 claims 1
- 101001125026 Homo sapiens Nucleotide-binding oligomerization domain-containing protein 2 Proteins 0.000 claims 1
- 101001117317 Homo sapiens Programmed cell death 1 ligand 1 Proteins 0.000 claims 1
- 229940122393 Hyaluronidase inhibitor Drugs 0.000 claims 1
- 102000037984 Inhibitory immune checkpoint proteins Human genes 0.000 claims 1
- 108091008026 Inhibitory immune checkpoint proteins Proteins 0.000 claims 1
- 102000007438 Interferon alpha-beta Receptor Human genes 0.000 claims 1
- 108010086140 Interferon alpha-beta Receptor Proteins 0.000 claims 1
- 241000124008 Mammalia Species 0.000 claims 1
- 206010027476 Metastases Diseases 0.000 claims 1
- 102000011931 Nucleoproteins Human genes 0.000 claims 1
- 108010061100 Nucleoproteins Proteins 0.000 claims 1
- 102100029441 Nucleotide-binding oligomerization domain-containing protein 2 Human genes 0.000 claims 1
- 108091034117 Oligonucleotide Proteins 0.000 claims 1
- 239000012270 PD-1 inhibitor Substances 0.000 claims 1
- 239000012668 PD-1-inhibitor Substances 0.000 claims 1
- 239000012271 PD-L1 inhibitor Substances 0.000 claims 1
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 claims 1
- 229940127395 Ribonucleotide Reductase Inhibitors Drugs 0.000 claims 1
- 108010078233 Thymalfasin Proteins 0.000 claims 1
- 108010046075 Thymosin Proteins 0.000 claims 1
- 102000007501 Thymosin Human genes 0.000 claims 1
- 102400000800 Thymosin alpha-1 Human genes 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 239000000556 agonist Substances 0.000 claims 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- 239000005557 antagonist Substances 0.000 claims 1
- 230000001028 anti-proliverative effect Effects 0.000 claims 1
- 229940034982 antineoplastic agent Drugs 0.000 claims 1
- 239000000074 antisense oligonucleotide Substances 0.000 claims 1
- 238000012230 antisense oligonucleotides Methods 0.000 claims 1
- 230000001580 bacterial effect Effects 0.000 claims 1
- 210000004027 cell Anatomy 0.000 claims 1
- 239000000134 cyclophilin inhibitor Substances 0.000 claims 1
- 239000002254 cytotoxic agent Substances 0.000 claims 1
- 231100000599 cytotoxic agent Toxicity 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 229940121360 farnesoid X receptor (fxr) agonists Drugs 0.000 claims 1
- 208000024386 fungal infectious disease Diseases 0.000 claims 1
- 230000012010 growth Effects 0.000 claims 1
- 208000002672 hepatitis B Diseases 0.000 claims 1
- 230000001939 inductive effect Effects 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- 239000003446 ligand Substances 0.000 claims 1
- 108020004999 messenger RNA Proteins 0.000 claims 1
- 230000009401 metastasis Effects 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 230000037361 pathway Effects 0.000 claims 1
- 229940121655 pd-1 inhibitor Drugs 0.000 claims 1
- 229940121656 pd-l1 inhibitor Drugs 0.000 claims 1
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 claims 1
- 230000035755 proliferation Effects 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 1
- 238000001959 radiotherapy Methods 0.000 claims 1
- 102000005962 receptors Human genes 0.000 claims 1
- 108020003175 receptors Proteins 0.000 claims 1
- 230000010076 replication Effects 0.000 claims 1
- 229930002330 retinoic acid Natural products 0.000 claims 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims 1
- 230000008685 targeting Effects 0.000 claims 1
- NZVYCXVTEHPMHE-ZSUJOUNUSA-N thymalfasin Chemical compound CC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NZVYCXVTEHPMHE-ZSUJOUNUSA-N 0.000 claims 1
- 229960004231 thymalfasin Drugs 0.000 claims 1
- LCJVIYPJPCBWKS-NXPQJCNCSA-N thymosin Chemical compound SC[C@@H](N)C(=O)N[C@H](CO)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CO)C(=O)N[C@H](CO)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@H]([C@H](C)O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@H](CCC(O)=O)C(O)=O LCJVIYPJPCBWKS-NXPQJCNCSA-N 0.000 claims 1
- 229960001727 tretinoin Drugs 0.000 claims 1
- 229960005486 vaccine Drugs 0.000 claims 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4433—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/10—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Biotechnology (AREA)
- Tropical Medicine & Parasitology (AREA)
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- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Claims (16)
1. Spoj formule (I),
[image]
uključujući njegove stereoizomere ili tautomerne oblike ili njegovu farmaceutski prihvatljivu sol, pri čemu
R1 je prsten izborno supstituiran s jednim ili više supstituenata odabranih iz halogena, CN, C1-6alkila, C1-6haloalkila, C3-6cikloalkila, C1-6heteroalkila, NRxRy, NRxC(=O)Ry, NRxCO2Ry, NRxC(=O)NRxRy, OC(=O)NRxRy, O-(6 do 10-člana arila), O-(5 do 10-člana heteroarila) i prstena;
R2, R3, R4, R5, R6, R7 i R11 neovisno se odabiru iz H, halogena, C1-4alkila i C1-4alkila supstituiranog s jednim ili više F;
R8 i R9 neovisno se odabiru iz H, C1-6alkila i C1-6heteroalkila, pri čemu je svaki C1-6alkil i C1-6heteroalkil izborno supstituiran s jednim ili više supstituenata odabranih iz C1-4alkila, OH, OCH3, -CO2H, -CO2C1-4alkil, C3-6heterocikla, arila i heteroarila,
pri čemu je C3-6heterocikl izborno supstituiran s jednim ili više supstituenata odabranih iz oksa, OH i CO2H;
pod uvjetom da R8 i R9 nisu oba H;
ili pri čemu su R8 i R9 povezani zajedno da tvore C3-6heterocikl izborno supstituiran s jednim ili više supstituenata odabranih iz C1-6alkila, oksa, OH i CO2H;
R10 se odabire iz H, CN, halogena, C1-6alkila, OC1-6alkila, C1-6alkila-CO2H, C1-6alkila-CO2-C1-6alkila, C1-6alkila-C(O)NH2, C1-6alkila-CO-NHC1-6alkila, C1-6alkila-C(O)N(C1-6alkila)2, C(=O)NRxRy, SO2-C1-6alkila, arila i heteroarila;
pri čemu su aril i heteroaril izborno supstituirani s jednim ili više supstituenata odabranih iz CN, halogena, C1-6alkila, OC1-6alkila, C1-6alkila-CO2H, C1-6alkila-CO2-C1-6alkila, C1-6alkila-C(O)NH2, C1-6alkila-CO-NHC1-6alkila, C1-6alkila-C(O)N(C1-6alkila)2, C(=O)NRxRy i SO2-C1-6alkila;
X je N ili CR12;
R12 se odabire iz H, F, Cl, CN, C(=O)NRxRy, arila i heteroarila,
pri čemu su aril i heteroaril izborno supstituirani s jednim ili više supstituenata odabranih iz CN, halogena, C1-6alkila, OC1-6alkila, C1-6alkila-CO2H, C1-6alkila-CO2-C1-6alkila, C1-6alkila-C(O)NH2, C1-6alkila-CO-NHC1-6alkila, C1-6alkila-C(O)N(C1-6alkila)2, C(=O)NRxRy i SO2-C1-6alkila; i
Rx i Ry neovisno se odabiru iz H i C1-6alkila.
2. Spoj prema zahtjevu 1, pri čemu se R2, R3, R4, R5, R6, R7 i R11 neovisno odabiru iz H i C1-4alkila ili
pri čemu je R6 C1-4alkil ili Cl ili
pri čemu je R6 Cl, a R2, R3, R4, R5, R7 i R11 su H.
3. Spoj prema bilo kojem od zahtjeva 1 ili 2, pri čemu je R1 formula (g-1),
[image]
4. Spoj prema bilo kojem od zahtjeva 1 – 3, pri čemu je R8 H, a R9 je C1-6alkil supstituiran s OH i CO2H ili pri čemu su R8 i R9 povezani zajedno da tvore C3-6heterocikl supstituiran s OH i CO2H.
5. Spoj prema zahtjevu 4, pri čemu je C3-6heterocikl pirolidin.
6. Spoj prema bilo kojem od zahtjeva 1 – 5, pri čemu je R10 CN, a X je N ili
pri čemu je R10 H a X je N.
7. Spoj prema bilo kojem od zahtjeva 1 – 6, pri čemu IC50 jednak ili manji od 5 µM.
8. Spoj prema zahtjevu 1, pri čemu je navedeni spoj odabran iz skupine koju čine
[image]
[image]
9. Spoj prema zahtjevu 1, pri čemu je navedeni spoj odabran iz skupine koju čine
[image]
[image]
10. Farmaceutski pripravak, koji sadrži spoj ili farmaceutski prihvatljivu sol prema bilo kojem od zahtjeva 1 – 9 i koji nadalje sadrži barem jedan farmaceutski prihvatljiv nositelj.
11. Farmaceutska kombinacija koja sadrži prvi spoj i drugi spoj kao kombinirani pripravak za istovremenu, odvojenu ili uzastopnu upotrebu u prevenciji ili liječenju infekcije ili raka u sisavca kojem je to potrebno, pri čemu je navedeni prvi spoj različit od navedenog drugog spoja, pri čemu je navedeni prvi spoj ili farmaceutski prihvatljiva sol prema bilo kojem od zahtjeva 1 – 9 ili farmaceutski pripravak prema zahtjevu 10, pri čemu je navedeni drugi spoj sastojak aktivan protiv navedene infekcije ili raka.
12. Farmaceutska kombinacija za upotrebu prema zahtjevu 11, pri čemu je navedeni drugi spoj inhibitor HBV-a odabran iz skupine koja se sastoji od kombiniranih lijekova protiv HBV-a, cjepiva protiv HBV-a, inhibitora HBV DNK polimeraze, imunomodulatora, modulatora TL-receptora (TLR), liganda receptora interferona alfa, inhibitora hijaluronidaze, inhibitora površinskog antigena hepatitisa B (HBsAg), inhibitora proteina 4 (ipi4) povezanog s citotoksičnim T-limfocitima, inhibitora ciklofilina, inhibitora ulaska HBV-a, antisens oligonukleotida koji cilja virusni mRNK, mali interferirajući RNK (siRNK) i modulatore endonukleaze ddRNKi, inhibitora ribonukleotid reduktaze, inhibitora antigena HBV E, inhibitori kovalentno zatvorenog kružnog DNK (cccDNK), agonista receptora farnezoida X, antitijela za HBV, antagonista kemokina CCR2, agonista timozina, citokina, modulatora nukleoproteina, simulatora gena 1 inducibilnog retinoičnom kiselinom, stimulatora NOD2, inhibitora fosfatidilinozitol 3-kinaze (PI3K), inhibitora puta indoleamin-2, 3-dioksigenaze (IDO), inhibitora PD-1, inhibitora PD-L1, rekombinantnog timozin alfe-1, inhibitora brutonove tirozin kinaze (BTK), inhibitora KDM-a, Inhibitora replikacije HBV-a, inhibitora arginaze i drugi lijekovi protiv HBV-a ili
pri čemu je navedeni drugi spoj agens protiv raka odabran iz grupe koja se sastoji od kemoterapijskih agensa, citotoksičnih agensa, radioterapijskih agensa, antineoplastičnih agensa i antiproliferativnih agensa.
13. Spoj ili farmaceutski prihvatljiva sol prema bilo kojem od zahtjeva 1 – 9 ili farmaceutski pripravak prema zahtjevu 10 ili farmaceutska kombinacija za upotrebu prema zahtjevima 11 ili 12, za upotrebu kao lijek.
14. Spoj ili farmaceutski prihvatljiva sol prema bilo kojem od zahtjeva 1 – 9 ili farmaceutski pripravak prema zahtjevu 10 ili farmaceutska kombinacija za uporabu prema zahtjevima 11 ili 12, za upotrebu u prevenciji ili liječenju zarazne bolesti, točnije bakterijske, virusne ili gljivične zarazne bolesti, točnije virusne zarazne bolesti u osobe kojoj je to potrebno ili
za upotrebu u liječenju raka, točnije za inhibiciju, rast, proliferaciju ili metastazu stanica raka u osobe kojoj je to potrebno.
15. Spoj ili farmaceutski prihvatljiva sol prema bilo kojem od zahtjeva 1 – 9 ili farmaceutski pripravak prema zahtjevu 10 ili farmaceutska kombinacija za upotrebu prema zahtjevima 11 ili 12, za upotrebu prema zahtjevima 14, pri čemu se spoj, farmaceutski prihvatljiva sol, farmaceutski pripravak ili farmaceutska kombinacija upotrebljava kao inhibitor imunosne kontrolne točke, točnije kao inhibitor kontrolne točke PDL1.
16. Postupak za pripremu spoja formule (I) prema bilo kojem od zahtjeva 1 – 9, koji se sastoji od reakcije spoja formule (II),
[image]
amina formule (III),
[image]
u prisutnosti natrijevog cijanoborhidrida, pri čemu su R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11 i X ovdje definirani.
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| EP19179072 | 2019-06-07 | ||
| PCT/EP2020/065646 WO2020245372A1 (en) | 2019-06-07 | 2020-06-05 | Heterocyclic immunomodulators as pdl1 checkpoint inhibitor |
| EP20730279.5A EP3980413B1 (en) | 2019-06-07 | 2020-06-05 | Heterocyclic immunomodulators as pdl1 checkpoint inhibitor |
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| US11046675B2 (en) * | 2017-03-27 | 2021-06-29 | Bristol-Myers Squibb Company | Substituted isoquionline derivatives as immunomudulators |
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2020
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| WO2020245372A1 (en) | 2020-12-10 |
| RS64681B1 (sr) | 2023-11-30 |
| ES2956866T3 (es) | 2023-12-29 |
| BR112021023780A2 (pt) | 2022-01-11 |
| CA3138494A1 (en) | 2020-12-10 |
| MA56098A (fr) | 2022-04-13 |
| MX2021015048A (es) | 2022-01-18 |
| EP3980413B1 (en) | 2023-07-19 |
| PL3980413T3 (pl) | 2023-12-27 |
| US20220259186A1 (en) | 2022-08-18 |
| KR20220017942A (ko) | 2022-02-14 |
| AU2020286962A1 (en) | 2022-02-03 |
| JP2022535879A (ja) | 2022-08-10 |
| HUE063236T2 (hu) | 2024-01-28 |
| EP3980413A1 (en) | 2022-04-13 |
| EP3980413C0 (en) | 2023-07-19 |
| MA56098B1 (fr) | 2023-10-31 |
| CN113966329A (zh) | 2022-01-21 |
| MD3980413T2 (ro) | 2023-12-31 |
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