RU2548905C2 - Терапевтические пептиды - Google Patents
Терапевтические пептиды Download PDFInfo
- Publication number
- RU2548905C2 RU2548905C2 RU2012121264/04A RU2012121264A RU2548905C2 RU 2548905 C2 RU2548905 C2 RU 2548905C2 RU 2012121264/04 A RU2012121264/04 A RU 2012121264/04A RU 2012121264 A RU2012121264 A RU 2012121264A RU 2548905 C2 RU2548905 C2 RU 2548905C2
- Authority
- RU
- Russia
- Prior art keywords
- amino acid
- peptide
- peptidomimetic
- groups
- group
- Prior art date
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Classifications
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- C—CHEMISTRY; METALLURGY
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- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
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- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
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- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/20—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/20—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals substituted additionally by nitrogen atoms, e.g. tryptophane
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/192—Radicals derived from carboxylic acids from aromatic carboxylic acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/02—Linear peptides containing at least one abnormal peptide link
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
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- Biophysics (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Oncology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Communicable Diseases (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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| PCT/GB2010/002024 WO2011051692A1 (en) | 2009-11-02 | 2010-11-02 | Therapeutic peptides |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| EP3974563A1 (en) | 2011-12-28 | 2022-03-30 | Chugai Seiyaku Kabushiki Kaisha | Cyclic peptides |
| JP7020910B2 (ja) | 2015-03-13 | 2022-02-16 | 中外製薬株式会社 | 改変アミノアシルtRNA合成酵素およびその用途 |
| GB201601868D0 (en) | 2016-02-02 | 2016-03-16 | Lytix Biopharma As | Methods |
| CN109071600A (zh) * | 2016-04-14 | 2018-12-21 | 道健康生活医药株式会社 | 淀粉样蛋白球体(aspd)结合抑制肽以及评价和筛选方法 |
| WO2018143145A1 (ja) | 2017-01-31 | 2018-08-09 | 中外製薬株式会社 | 無細胞翻訳系におけるペプチドの合成方法 |
| GB201705255D0 (en) * | 2017-03-31 | 2017-05-17 | Univ I Tromsø - Norges Arktiske Univ | Bioactive cyclic compounds |
| WO2018188761A1 (en) | 2017-04-13 | 2018-10-18 | Lytix Biopharma As | Method of reducing population size of tregs and/or mdscs |
| US11542299B2 (en) | 2017-06-09 | 2023-01-03 | Chugai Seiyaku Kabushiki Kaisha | Method for synthesizing peptide containing N-substituted amino acid |
| JP7411414B2 (ja) | 2017-12-15 | 2024-01-11 | 中外製薬株式会社 | ペプチドの製造方法、及び塩基の処理方法 |
| KR20250119653A (ko) | 2018-11-07 | 2025-08-07 | 추가이 세이야쿠 가부시키가이샤 | O-치환 세린 유도체의 제조 방법 |
| EP3889164A4 (en) | 2018-11-30 | 2022-11-02 | Chugai Seiyaku Kabushiki Kaisha | METHOD FOR DEPROTECTION AND METHOD FOR RESIN REMOVAL IN A SOLID PHASE REACTION OF A PEPTIDE COMPOUND OR AN AMIDE COMPOUND, AND METHOD FOR PRODUCTION OF A PEPTIDE COMPOUND |
| JP7472101B2 (ja) | 2019-03-15 | 2024-04-22 | 中外製薬株式会社 | 芳香族アミノ酸誘導体の製造方法 |
| CN110294793B (zh) * | 2019-06-24 | 2023-10-27 | 合肥科生景肽生物科技有限公司 | Sumo荧光探针及其制备方法 |
| JP6880352B1 (ja) | 2019-11-07 | 2021-06-02 | 中外製薬株式会社 | Kras阻害作用を有する環状ペプチド化合物 |
| CN114790151B (zh) * | 2022-02-14 | 2023-03-31 | 湖南省湘中制药有限公司 | 一种2-氰基-2-丙戊酸甲酯的复合催化制备方法 |
| KR20250122523A (ko) | 2022-12-20 | 2025-08-13 | 리틱스 바이오파마 에이에스 | 종양 용해성 펩티드 및 키토산을 포함하는 조성물 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992012168A1 (en) * | 1990-12-27 | 1992-07-23 | Abbott Laboratories | Modified hexa- and heptapeptide anaphylatoxin receptor ligands |
| DE102006018080A1 (de) * | 2006-04-13 | 2007-10-18 | Aicuris Gmbh & Co. Kg | Lysobactinamide |
| EP2105433A1 (en) * | 2008-03-18 | 2009-09-30 | Technische Universität Dresden | Modular scaffold for the design of specific molecules for the use as peptidomimetics and inhibitors of protein interaction |
| RU2468033C2 (ru) * | 2006-07-10 | 2012-11-27 | Пба3 БиоМед ГмбХ | Антибактериальные пептиды |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4342705A (en) | 1979-11-23 | 1982-08-03 | Monsanto Company | Methylene thioethers |
| AU565221B2 (en) | 1982-06-03 | 1987-09-10 | Montedison S.P.A. | 2-(1,2,4-triazol-1-yl) propanone derivatives |
| IT1161927B (it) | 1983-03-31 | 1987-03-18 | Montedison Spa | Furano-derivati ad attivita' fungicida |
| DK523288A (da) | 1987-10-06 | 1989-04-07 | Hoffmann La Roche | Aminosyrederivater |
| CA1328333C (en) | 1988-03-04 | 1994-04-05 | Quirico Branca | Amino acid derivatives |
| CA2088195A1 (en) | 1990-08-31 | 1992-03-01 | David C. Horwell | Cholecystokinin antagonists, their preparation and therapeutic use |
| US5593967A (en) | 1990-08-31 | 1997-01-14 | Warner-Lambert Company | Cholecystokinin antagonists, their preparation and therapeutic use |
| US5885782A (en) | 1994-09-13 | 1999-03-23 | Nce Pharmaceuticals, Inc. | Synthetic antibiotics |
| CZ297544B6 (cs) | 1996-01-02 | 2007-02-07 | Aventis Pharmaceuticals Inc. | Substituované N-[(aminoiminomethyl)-fenyl]propylamidy nebo N-[(aminomethyl)fenyl]propylamidy |
| US6323227B1 (en) | 1996-01-02 | 2001-11-27 | Aventis Pharmaceuticals Products Inc. | Substituted N-[(aminoiminomethyl or aminomethyl)phenyl]propyl amides |
| US6080767A (en) | 1996-01-02 | 2000-06-27 | Aventis Pharmaceuticals Products Inc. | Substituted n-[(aminoiminomethyl or aminomethyl)phenyl]propyl amides |
| JP3734907B2 (ja) | 1996-12-19 | 2006-01-11 | 富士写真フイルム株式会社 | 現像処理方法 |
| GB0724951D0 (en) * | 2007-12-20 | 2008-01-30 | Lytix Biopharma As | Compounds |
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2009
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2010
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992012168A1 (en) * | 1990-12-27 | 1992-07-23 | Abbott Laboratories | Modified hexa- and heptapeptide anaphylatoxin receptor ligands |
| DE102006018080A1 (de) * | 2006-04-13 | 2007-10-18 | Aicuris Gmbh & Co. Kg | Lysobactinamide |
| RU2468033C2 (ru) * | 2006-07-10 | 2012-11-27 | Пба3 БиоМед ГмбХ | Антибактериальные пептиды |
| EP2105433A1 (en) * | 2008-03-18 | 2009-09-30 | Technische Universität Dresden | Modular scaffold for the design of specific molecules for the use as peptidomimetics and inhibitors of protein interaction |
Non-Patent Citations (1)
| Title |
|---|
| STROEM M B ET AL: "The pharmacophore of short cationic antibacterial peptides", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, 2003, vol. 46, no. 9, pages 1567-1570 . HANSEN TERKEL ET AL: "Antimicrobial activity of small beta-peptidomimetics based on the pharmacophore model of short cationic antimicrobial peptides.", JOURNAL OF MEDICINAL CHEMISTRY,2010, vol. 53, no. 2, pages 595-606 * |
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| DK2496596T3 (en) | 2017-04-03 |
| EP2496596A1 (en) | 2012-09-12 |
| JP2013509389A (ja) | 2013-03-14 |
| CA2777749C (en) | 2019-08-06 |
| ES2621188T3 (es) | 2017-07-03 |
| GB0919194D0 (en) | 2009-12-16 |
| JP5810090B2 (ja) | 2015-11-11 |
| RU2015111706A3 (enExample) | 2018-10-29 |
| US20130035296A1 (en) | 2013-02-07 |
| KR20120104986A (ko) | 2012-09-24 |
| BR112012010333A2 (pt) | 2016-03-29 |
| AU2010311186B2 (en) | 2015-09-24 |
| RU2676713C2 (ru) | 2019-01-10 |
| RU2012121264A (ru) | 2013-12-10 |
| WO2011051692A1 (en) | 2011-05-05 |
| CN102762586A (zh) | 2012-10-31 |
| CN102762586B (zh) | 2016-10-05 |
| PL2496596T3 (pl) | 2017-08-31 |
| AU2010311186A1 (en) | 2012-05-31 |
| US8809280B2 (en) | 2014-08-19 |
| KR101730680B1 (ko) | 2017-04-26 |
| NZ599791A (en) | 2014-10-31 |
| RU2015111706A (ru) | 2015-11-10 |
| EP2496596B1 (en) | 2017-01-11 |
| CA2777749A1 (en) | 2011-05-05 |
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