HRP20170403T1 - SUPSTITUIRANI BENZOAZEPINI KAO MODULATORI TOLL-u SLIČNIH RECEPTORA - Google Patents
SUPSTITUIRANI BENZOAZEPINI KAO MODULATORI TOLL-u SLIČNIH RECEPTORA Download PDFInfo
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- HRP20170403T1 HRP20170403T1 HRP20170403TT HRP20170403T HRP20170403T1 HR P20170403 T1 HRP20170403 T1 HR P20170403T1 HR P20170403T T HRP20170403T T HR P20170403TT HR P20170403 T HRP20170403 T HR P20170403T HR P20170403 T1 HRP20170403 T1 HR P20170403T1
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- hydrogen
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Links
- 102000002689 Toll-like receptor Human genes 0.000 title 1
- 108020000411 Toll-like receptor Proteins 0.000 title 1
- 150000008038 benzoazepines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 15
- 229910052739 hydrogen Inorganic materials 0.000 claims 12
- 239000001257 hydrogen Substances 0.000 claims 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 10
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims 6
- 229920006395 saturated elastomer Polymers 0.000 claims 6
- 150000003839 salts Chemical class 0.000 claims 4
- 125000000217 alkyl group Chemical group 0.000 claims 3
- 201000010099 disease Diseases 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 125000006711 (C2-C12) alkynyl group Chemical group 0.000 claims 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims 1
- 125000001960 7 membered carbocyclic group Chemical group 0.000 claims 1
- 208000023275 Autoimmune disease Diseases 0.000 claims 1
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 1
- 208000024172 Cardiovascular disease Diseases 0.000 claims 1
- 208000035473 Communicable disease Diseases 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 206010020751 Hypersensitivity Diseases 0.000 claims 1
- 206010061598 Immunodeficiency Diseases 0.000 claims 1
- 208000029462 Immunodeficiency disease Diseases 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 206010040047 Sepsis Diseases 0.000 claims 1
- 206010052779 Transplant rejections Diseases 0.000 claims 1
- 230000007815 allergy Effects 0.000 claims 1
- 208000006673 asthma Diseases 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 230000003176 fibrotic effect Effects 0.000 claims 1
- 230000007813 immunodeficiency Effects 0.000 claims 1
- 208000015181 infectious disease Diseases 0.000 claims 1
- 208000027866 inflammatory disease Diseases 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
Classifications
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- 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
- C07D403/10—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 carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
-
- 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
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- 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
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Claims (15)
1. Spoj s formulom I, ili njegova farmaceutski prihvatljiva sol:
[image]
,
naznačen time što
[image]
je dvostruka veza ili jednostruka veza;
R2 i R3 se neovisno bira između H i C1-C6 alkila, ili su R2 i R3 povezani kako bi tvorili zasićeni 3 do 7-eročlani karbocikl;
jedan od R7 i R8 je
[image]
ili
[image]
,
a drugi je vodik;
R4 je -NRcRd ili -OR10;
Rc i Rd su C1-C6 alkil, koji može biti supstituiran s jednim ili više -OH;
R10 je C1-C12 alkil, koji može biti supstituiran s jednim ili više -OH;
Z je C i
[image]
je dvostruka veza, ili Z je N, a
[image]
je jednostruka veza;
Ra i Rb se neovisno bira između H, C1-C12 alkila, C2-C10 alkenila, C2-C12 alkinila i Re, gdje C1-C12 alkil može biti supstituiran s jednim ili više -OR10, ili Re;
Re se bira između -NH2, -NH(C1-C12 alkil) i -N(C1-C12 alkil)2;
R1 je odsutan kada
[image]
je dvostruka veza, ili kada
[image]
je jednostruka veza, N1-R1 i jedan od Ra ili Rb su povezani kako bi tvorili zasićeni, djelomično nezasićeni ili nezasićeni 5-7-eročlani heterociklički prsten, a drugi od Ra ili Rb može biti vodik ili je po potrebi odsutan zbog nezasićenosti prstena; i
gdje vrijedi najmanje jedna od slijedećih točaka A-D:
A) R7 nije vodik;
B) R8 nije vodik i najmanje jedan od Ra i Rb nije vodik;
C) Z je N; ili
D) N1-R1 i jedan od Ra ili Rb su povezani kako bi tvorili zasićeni, djelomično nezasićeni ili nezasićeni 5-7-eročlani heterociklički prsten.
2. Spoj u skladu s patentnim zahtjevom 1, naznačen time što je R7
[image]
ili
[image]
.
3. Spoj u skladu s patentnim zahtjevom 1 ili 2, naznačen time što najmanje jedan od Ra i Rb nije vodik; ili je jedan od Ra i Rb C1-C12 alkil, a drugi od Ra i Rb je vodik; ili je jedan od Ra i Rb C1-C12 alkil, supstituiran s Re; ili su Ra i Rb oba C1-C12 alkil; ili je jedan od Ra i Rb Re, a drugi od Ra i Rb je vodik.
4. Spoj u skladu s patentnim zahtjevom 1, naznačen time što R8 nije vodik.
5. Spoj u skladu s patentnim zahtjevom 1, naznačen time što su N1 i jedan od Ra ili Rb povezani kako bi tvorili zasićeni, djelomično nezasićeni ili nezasićeni 5-7-eročlani heterociklički prsten, a drugi od Ra ili Rb je vodik ili je po potrebi odsutan zbog nezasićenosti prstena.
6. Spoj u skladu s patentnim zahtjevom 5, naznačen time što su N1 i jedan od Ra ili Rb povezani kako bi tvorili zasićeni, djelomično nezasićeni ili nezasićeni 5-eročlani heterociklički prsten.
7. Spoj u skladu s patentnim zahtjevom 6, naznačen time što su N1 i jedan od Ra ili Rb povezani kako bi tvorili
[image]
ili
[image]
.
8. Spoj u skladu s patentnim zahtjevom 1, naznačen time što najmanje jedan od R2 i R3 nije vodik; ili su R2 i R3 povezani kako bi tvorili zasićeni karbocikl.
9. Spoj u skladu s patentnim zahtjevom 8, naznačen time što su R2 i R3 povezani kako bi tvorili ciklopropil.
10. Spoj u skladu s patentnim zahtjevom 1, naznačen time što je Z N.
11. Spoj u skladu s patentnim zahtjevom 1, naznačen time što je R4 -OR10, a R10 je alkil; ili je R4 -NRcRd, a Rc i Rd su oba alkil.
12. Spoj u skladu s patentnim zahtjevom 11, naznačen time što je R4 -O-etil ili -N(propil)2.
13. Spoj u skladu s patentnim zahtjevom 1, naznačen time što se bira između
[image]
[image]
ili njihovih farmaceutski prihvatljivih soli.
14. Farmaceutski pripravak, naznačen time što sadrži spoj u skladu s bilo kojim od patentnih zahtjeva 1-13 ili, njegovu farmaceutski prihvatljivu sol, kao i farmaceutski prihvatljiv razrjeđivač ili podlogu.
15. Spoj u skladu s bilo kojim od patentnih zahtjeva 1-13 ili, njegova farmaceutski prihvatljiva sol, naznačen time što je namijenjen upotrebi u liječenju stanja koje se bira između raka, bolesti povezane s imunosnim kompleksom, autoimune bolesti, zarazne bolesti, upalnog poremećaja, imunodeficijencije, odbacivanja presatka, reakcije presatka prema domaćinu, alergije, kardiovaskularne bolesti, fibrotične bolesti, astme i sepse.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161432070P | 2011-01-12 | 2011-01-12 | |
| EP12733896.0A EP2663555B1 (en) | 2011-01-12 | 2012-01-12 | Substituted benzoazepines as toll-like receptor modulators |
| PCT/US2012/021116 WO2012097177A2 (en) | 2011-01-12 | 2012-01-12 | Substituted benzoazepines as toll-like receptor modulators |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20170403T1 true HRP20170403T1 (hr) | 2017-05-19 |
Family
ID=46507673
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20170403TT HRP20170403T1 (hr) | 2011-01-12 | 2017-03-10 | SUPSTITUIRANI BENZOAZEPINI KAO MODULATORI TOLL-u SLIČNIH RECEPTORA |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US20140088085A1 (hr) |
| EP (2) | EP3207930A1 (hr) |
| JP (2) | JP5985510B2 (hr) |
| CN (2) | CN103562201B (hr) |
| AU (1) | AU2012205490B2 (hr) |
| BR (1) | BR112013017947A2 (hr) |
| CA (1) | CA2824786A1 (hr) |
| DK (1) | DK2663555T3 (hr) |
| ES (1) | ES2620605T3 (hr) |
| HR (1) | HRP20170403T1 (hr) |
| HU (1) | HUE032638T2 (hr) |
| MX (1) | MX348935B (hr) |
| PL (1) | PL2663555T4 (hr) |
| PT (1) | PT2663555T (hr) |
| WO (1) | WO2012097177A2 (hr) |
Families Citing this family (146)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2663550B1 (en) * | 2011-01-12 | 2016-12-14 | VentiRx Pharmaceuticals, Inc. | Substituted benzoazepines as toll-like receptor modulators |
| CN112587658A (zh) | 2012-07-18 | 2021-04-02 | 博笛生物科技有限公司 | 癌症的靶向免疫治疗 |
| CN105899537A (zh) | 2014-01-10 | 2016-08-24 | 博笛生物科技（北京）有限公司 | 靶向表达egfr的肿瘤的化合物和组合物 |
| US10413565B2 (en) | 2014-04-30 | 2019-09-17 | Northwestern University | Nanostructures for modulating intercellular communication and uses thereof |
| TR201908550T4 (tr) | 2014-06-04 | 2019-07-22 | Exicure Inc | Profilaktik veya terapötik uygulamalar için lipozomal sferik nükleik asitler tarafından immün modülatörlerin çok değerlikli teslimi. |
| CN112546231A (zh) | 2014-07-09 | 2021-03-26 | 博笛生物科技有限公司 | 用于治疗癌症的联合治疗组合物和联合治疗方法 |
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| PL2663555T4 (pl) | 2017-08-31 |
| JP2016199582A (ja) | 2016-12-01 |
| BR112013017947A2 (pt) | 2018-12-18 |
| ES2620605T3 (es) | 2017-06-29 |
| JP2014503556A (ja) | 2014-02-13 |
| WO2012097177A2 (en) | 2012-07-19 |
| PT2663555T (pt) | 2017-03-23 |
| HUE032638T2 (en) | 2017-10-30 |
| US20140088085A1 (en) | 2014-03-27 |
| AU2012205490B2 (en) | 2017-02-02 |
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