RU2328486C2 - Производные 2-пиридона в качестве ингибиторов нейтрофильной эластазы - Google Patents
Производные 2-пиридона в качестве ингибиторов нейтрофильной эластазы Download PDFInfo
- Publication number
- RU2328486C2 RU2328486C2 RU2005113168/04A RU2005113168A RU2328486C2 RU 2328486 C2 RU2328486 C2 RU 2328486C2 RU 2005113168/04 A RU2005113168/04 A RU 2005113168/04A RU 2005113168 A RU2005113168 A RU 2005113168A RU 2328486 C2 RU2328486 C2 RU 2328486C2
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- RU
- Russia
- Prior art keywords
- alkyl
- formula
- compound
- independently selected
- phenyl
- Prior art date
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- 108010028275 Leukocyte Elastase Proteins 0.000 title abstract 2
- 102000016799 Leukocyte elastase Human genes 0.000 title abstract 2
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical class OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 title abstract 2
- 239000003112 inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract 17
- 230000000694 effects Effects 0.000 claims abstract 5
- 238000000034 method Methods 0.000 claims abstract 2
- 125000000217 alkyl group Chemical group 0.000 claims 24
- 229910052799 carbon Inorganic materials 0.000 claims 12
- 125000005842 heteroatom Chemical group 0.000 claims 10
- 229910052760 oxygen Inorganic materials 0.000 claims 10
- 229910052717 sulfur Inorganic materials 0.000 claims 10
- 229910052739 hydrogen Inorganic materials 0.000 claims 9
- 150000003839 salts Chemical class 0.000 claims 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 6
- 125000003545 alkoxy group Chemical group 0.000 claims 5
- 229910052757 nitrogen Inorganic materials 0.000 claims 5
- 229910052736 halogen Inorganic materials 0.000 claims 4
- 150000002367 halogens Chemical class 0.000 claims 4
- 125000001072 heteroaryl group Chemical group 0.000 claims 4
- 229920006395 saturated elastomer Polymers 0.000 claims 4
- 125000001424 substituent group Chemical group 0.000 claims 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- 125000000623 heterocyclic group Chemical group 0.000 claims 3
- 102000016387 Pancreatic elastase Human genes 0.000 claims 2
- 108010067372 Pancreatic elastase Proteins 0.000 claims 2
- 125000002252 acyl group Chemical group 0.000 claims 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 230000003448 neutrophilic effect Effects 0.000 claims 2
- 230000003287 optical effect Effects 0.000 claims 2
- 238000011282 treatment Methods 0.000 claims 2
- RCMAWNRDRWSYIH-UHFFFAOYSA-N 5,6-dimethyl-2-oxo-1-phenyl-n-(2-phenylethyl)pyridine-3-carboxamide Chemical compound O=C1N(C=2C=CC=CC=2)C(C)=C(C)C=C1C(=O)NCCC1=CC=CC=C1 RCMAWNRDRWSYIH-UHFFFAOYSA-N 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 230000009286 beneficial effect Effects 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 208000027866 inflammatory disease Diseases 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- 125000005647 linker group Chemical group 0.000 claims 1
- 125000002950 monocyclic group Chemical group 0.000 claims 1
- CDEBWUKPPGESTE-UHFFFAOYSA-N n-(2-hydroxyethyl)-2,4-dioxo-3-phenyl-1h-pyrimidine-5-carboxamide Chemical compound O=C1C(C(=O)NCCO)=CNC(=O)N1C1=CC=CC=C1 CDEBWUKPPGESTE-UHFFFAOYSA-N 0.000 claims 1
- HADHYSLATZGMOO-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-2,4-dioxo-3-phenyl-1h-pyrimidine-5-carboxamide Chemical compound O=C1C(C(=O)NCCN(C)C)=CNC(=O)N1C1=CC=CC=C1 HADHYSLATZGMOO-UHFFFAOYSA-N 0.000 claims 1
- DJADWRUXZAZMCS-UHFFFAOYSA-N n-benzyl-5,6-dimethyl-2-oxo-1-phenylpyridine-3-carboxamide Chemical compound O=C1N(C=2C=CC=CC=2)C(C)=C(C)C=C1C(=O)NCC1=CC=CC=C1 DJADWRUXZAZMCS-UHFFFAOYSA-N 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 101000851058 Homo sapiens Neutrophil elastase Proteins 0.000 abstract 1
- 238000007905 drug manufacturing Methods 0.000 abstract 1
- 102000052502 human ELANE Human genes 0.000 abstract 1
- 239000008177 pharmaceutical agent Substances 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
-
- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 directly attached to ring carbon atoms
- C07D211/86—Oxygen atoms
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
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- C07D239/20—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
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- C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/557—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms, e.g. orotic acid
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Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0203348-8 | 2002-11-12 | ||
| SE0203348A SE0203348D0 (sv) | 2002-11-12 | 2002-11-12 | Novel compounds |
| SE0300388-6 | 2003-02-12 | ||
| SE0300388A SE0300388D0 (sv) | 2003-02-12 | 2003-02-12 | Novel compounds |
| SE0302120-1 | 2003-07-22 | ||
| SE0302120A SE0302120D0 (sv) | 2003-07-22 | 2003-07-22 | Novel compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2005113168A RU2005113168A (ru) | 2006-01-20 |
| RU2328486C2 true RU2328486C2 (ru) | 2008-07-10 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
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| US8927550B2 (en) | 2009-10-27 | 2015-01-06 | Boehringer Ingelheim International Gmbh | Heterocyclic compounds as CCR1 receptor antagonists |
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| AU2010328480A1 (en) * | 2009-12-08 | 2012-05-17 | Boehringer Ingelheim International Gmbh | Process for synthesis of intermediates useful for making substituted indazole and azaindazole compounds |
| US8871786B2 (en) | 2010-04-30 | 2014-10-28 | Boehringer Ingelheim International Gmbh | Azaindazole amide compounds as CCR1 receptor antagonists |
| WO2012087782A1 (en) | 2010-12-23 | 2012-06-28 | Boehringer Ingelheim International Gmbh | Pyrazolopiperidine compounds as ccr1 receptor antagonists |
| TWI549943B (zh) * | 2011-03-09 | 2016-09-21 | 杜邦股份有限公司 | 除草之含側氧與磺酸基(sulfono)雙氮雜環 |
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| EP2562174A1 (de) * | 2011-08-24 | 2013-02-27 | Bayer Cropscience AG | Herbizid wirksame 6-Oxo-1,6-dihydropyrimidin-5-carboxamide und 2-Oxo-1,2-dihydropyridin-3-carboxamide |
| US9206128B2 (en) | 2011-11-18 | 2015-12-08 | Constellation Pharmaceuticals, Inc. | Modulators of methyl modifying enzymes, compositions and uses thereof |
| EP2780013A4 (en) | 2011-11-18 | 2015-07-01 | Constellation Pharmaceuticals Inc | MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF |
| EP2812001B1 (en) | 2012-02-10 | 2017-06-14 | Constellation Pharmaceuticals, Inc. | Modulators of methyl modifying enzymes, compositions and uses thereof |
| US20140057920A1 (en) * | 2012-08-23 | 2014-02-27 | Boehringer Ingelheim International Gmbh | Substituted 4-pyridones and their use as inhibitors of neutrophil elastase activity |
| US9102624B2 (en) | 2012-08-23 | 2015-08-11 | Boehringer Ingelheim International Gmbh | Substituted 4-pyridones and their use as inhibitors of neutrophil elastase activity |
| US20140057926A1 (en) | 2012-08-23 | 2014-02-27 | Boehringer Ingelheim International Gmbh | Substituted 4-pyridones and their use as inhibitors of neutrophil elastase activity |
| JP5799117B2 (ja) * | 2013-02-05 | 2015-10-21 | 大日本住友製薬株式会社 | ウラシル誘導体からなる医薬 |
| EP2970305B1 (en) | 2013-03-15 | 2017-02-22 | Constellation Pharmaceuticals, Inc. | Modulators of methyl modifying enzymes, compositions and uses thereof |
| EP3033334A1 (en) | 2013-08-15 | 2016-06-22 | Constellation Pharmaceuticals, Inc. | Indole derivatives as modulators of methyl modifying enzymes, compositions and uses thereof |
| US9221807B2 (en) * | 2014-02-21 | 2015-12-29 | Boehringer Ingelheim International Gmbh | Substituted pyridones and pyrazinones and their use as inhibitors of neutrophil elastase activity |
| PT3174852T (pt) * | 2014-07-30 | 2018-10-23 | Abac Therapeutics S L | Aril-hidrazidas contendo uma unidade 2-piridona como agentes antibacterianos seletivos |
| WO2017040190A1 (en) | 2015-08-28 | 2017-03-09 | Constellation Pharmaceuticals, Inc. | Crystalline forms of (r)-n-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1h-indole-3-carboxamide |
| EP3529242A1 (en) | 2016-10-19 | 2019-08-28 | Constellation Pharmaceuticals, Inc. | Synthesis of inhibitors of ezh2 |
| US11130740B2 (en) | 2017-04-25 | 2021-09-28 | Arbutus Biopharma Corporation | Substituted 2,3-dihydro-1H-indene analogs and methods using same |
| US11472774B2 (en) * | 2018-02-01 | 2022-10-18 | The University Of Sydney | Anti-cancer compounds |
| CN111683976B (zh) | 2018-02-05 | 2022-11-18 | 生物辐射实验室股份有限公司 | 具有阴离子交换-疏水混合模式配体的色谱树脂 |
| US12083118B2 (en) | 2018-03-29 | 2024-09-10 | Arbutus Biopharma Corporation | Substituted 1,1′-biphenyl compounds, analogues thereof, and methods using same |
| CA3154761A1 (en) | 2019-09-17 | 2021-03-25 | Mereo Biopharma 4 Limited | Alvelestat for use in the treatment of graft rejection, bronchiolitis obliterans syndrome and graft versus host disease |
| SI4106757T1 (sl) | 2020-04-16 | 2023-11-30 | Mereo Biopharma 4 Limited | Postopki, ki vključujejo zaviralec nevtrofilne elastaze alvelestat, za zdravljenje bolezni dihal, ki jo sproži pomanjkanje antitripsina alfa-1 |
| WO2023067103A1 (en) | 2021-10-20 | 2023-04-27 | Mereo Biopharma 4 Limited | Neutrophil elastase inhibitors for use in the treatment of fibrosis |
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| SE0302486D0 (sv) * | 2003-09-18 | 2003-09-18 | Astrazeneca Ab | Novel compounds |
-
2003
- 2003-11-06 TW TW092131093A patent/TW200500341A/zh unknown
- 2003-11-10 MY MYPI20034290A patent/MY137133A/en unknown
- 2003-11-11 PT PT03811170T patent/PT1562902E/pt unknown
- 2003-11-11 CA CA002504766A patent/CA2504766A1/en not_active Abandoned
- 2003-11-11 NZ NZ539787A patent/NZ539787A/en unknown
- 2003-11-11 AT AT03811170T patent/ATE325096T1/de not_active IP Right Cessation
- 2003-11-11 ES ES03811170T patent/ES2262029T3/es not_active Expired - Lifetime
- 2003-11-11 WO PCT/SE2003/001739 patent/WO2004043924A1/en not_active Ceased
- 2003-11-11 BR BR0316081-5A patent/BR0316081A/pt not_active IP Right Cessation
- 2003-11-11 AU AU2003276802A patent/AU2003276802B2/en not_active Ceased
- 2003-11-11 MX MXPA05004818A patent/MXPA05004818A/es active IP Right Grant
- 2003-11-11 DK DK03811170T patent/DK1562902T3/da active
- 2003-11-11 PL PL376957A patent/PL376957A1/pl not_active Application Discontinuation
- 2003-11-11 KR KR1020057008383A patent/KR20050086516A/ko not_active Ceased
- 2003-11-11 DE DE60305061T patent/DE60305061T2/de not_active Expired - Fee Related
- 2003-11-11 EP EP03811170A patent/EP1562902B1/en not_active Expired - Lifetime
- 2003-11-11 RU RU2005113168/04A patent/RU2328486C2/ru not_active IP Right Cessation
- 2003-11-11 US US10/534,720 patent/US20060035938A1/en not_active Abandoned
- 2003-11-11 JP JP2005506687A patent/JP2006513261A/ja active Pending
- 2003-11-11 SI SI200330314T patent/SI1562902T1/sl unknown
- 2003-11-12 AR ARP030104153A patent/AR042024A1/es unknown
-
2005
- 2005-05-26 IS IS7867A patent/IS2478B/is unknown
- 2005-06-10 NO NO20052818A patent/NO20052818L/no not_active Application Discontinuation
-
2006
- 2006-07-27 CY CY20061101039T patent/CY1106130T1/el unknown
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Also Published As
| Publication number | Publication date |
|---|---|
| MXPA05004818A (es) | 2005-07-22 |
| EP1562902B1 (en) | 2006-05-03 |
| PT1562902E (pt) | 2006-08-31 |
| WO2004043924A1 (en) | 2004-05-27 |
| PL376957A1 (pl) | 2006-01-09 |
| TW200500341A (en) | 2005-01-01 |
| AU2003276802B2 (en) | 2007-03-08 |
| HK1079200A1 (en) | 2006-03-31 |
| KR20050086516A (ko) | 2005-08-30 |
| AR042024A1 (es) | 2005-06-08 |
| EP1562902A1 (en) | 2005-08-17 |
| ATE325096T1 (de) | 2006-06-15 |
| CA2504766A1 (en) | 2004-05-27 |
| CY1106130T1 (el) | 2011-06-08 |
| DK1562902T3 (da) | 2006-08-14 |
| NO20052818L (no) | 2005-07-11 |
| DE60305061D1 (de) | 2006-06-08 |
| MY137133A (en) | 2008-12-31 |
| AU2003276802A1 (en) | 2004-06-03 |
| US20060035938A1 (en) | 2006-02-16 |
| DE60305061T2 (de) | 2006-12-07 |
| IS2478B (is) | 2008-12-15 |
| BR0316081A (pt) | 2005-09-27 |
| JP2006513261A (ja) | 2006-04-20 |
| ES2262029T3 (es) | 2006-11-16 |
| SI1562902T1 (sl) | 2006-08-31 |
| IS7867A (is) | 2005-05-26 |
| RU2005113168A (ru) | 2006-01-20 |
| NZ539787A (en) | 2006-11-30 |
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