KR101500528B1 - 새로운 비-선택적 소마토스타틴 유사체 - Google Patents
새로운 비-선택적 소마토스타틴 유사체 Download PDFInfo
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- KR101500528B1 KR101500528B1 KR1020107010880A KR20107010880A KR101500528B1 KR 101500528 B1 KR101500528 B1 KR 101500528B1 KR 1020107010880 A KR1020107010880 A KR 1020107010880A KR 20107010880 A KR20107010880 A KR 20107010880A KR 101500528 B1 KR101500528 B1 KR 101500528B1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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Landscapes
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| ITMI2007A002266 | 2007-12-03 | ||
| ITMI20072266 ITMI20072266A1 (it) | 2007-12-03 | 2007-12-03 | Nuovi analoghi non selettivi di somatostatina |
| EP07425778.3 | 2007-12-07 | ||
| EP07425778A EP2067786A1 (en) | 2007-12-07 | 2007-12-07 | Novel non selective analogs of somatostatin |
| PCT/EP2008/066081 WO2009071460A2 (en) | 2007-12-03 | 2008-11-24 | New non-selective somatostatin analogues |
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| KR20100103464A KR20100103464A (ko) | 2010-09-27 |
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| PL2225271T3 (pl) * | 2007-12-03 | 2013-12-31 | Italfarmaco Spa | Nowe nieselektywne analogi somatostatyny |
| CA2807685C (en) | 2010-08-13 | 2020-10-06 | Aileron Therapeutics, Inc. | P53 derived peptidomimetic macrocycle |
| CA2847336C (en) * | 2011-09-04 | 2021-09-07 | Glytech, Inc. | Glycosylated polypeptide and drug composition containing said polypeptide |
| TW201806968A (zh) | 2011-10-18 | 2018-03-01 | 艾利倫治療公司 | 擬肽巨環化合物 |
| BR112014020103A2 (pt) | 2012-02-15 | 2018-10-09 | Aileron Therapeutics, Inc. | macrociclos peptidomiméticos |
| CA2864120A1 (en) | 2012-02-15 | 2013-08-22 | Aileron Therapeutics, Inc. | Triazole-crosslinked and thioether-crosslinked peptidomimetic macrocycles |
| KR20150082307A (ko) | 2012-11-01 | 2015-07-15 | 에일러론 테라퓨틱스 인코포레이티드 | 이치환 아미노산 및 이의 제조 및 사용 방법 |
| US20160129089A1 (en) * | 2013-06-13 | 2016-05-12 | Antisense Therapeutics Ltd | Combination therapy |
| CN103467575B (zh) * | 2013-08-22 | 2016-03-02 | 深圳翰宇药业股份有限公司 | 一种帕西瑞肽的制备方法 |
| CN103641894B (zh) * | 2013-12-06 | 2015-10-28 | 深圳翰宇药业股份有限公司 | 一种治疗库欣病的多肽药物的制备方法 |
| MX2017003797A (es) | 2014-09-24 | 2017-06-15 | Aileron Therapeutics Inc | Macrociclos peptidomimeticos y usos de los mismos. |
| CN104447962B (zh) * | 2014-12-29 | 2018-07-17 | 成都圣诺生物科技股份有限公司 | 一种合成帕瑞肽的方法 |
| US10253067B2 (en) | 2015-03-20 | 2019-04-09 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| CN117122707A (zh) * | 2018-09-25 | 2023-11-28 | 意大利国际先进加速器应用有限公司 | 联合疗法 |
| GB201816637D0 (en) | 2018-10-12 | 2018-11-28 | Heptares Therapeutics Ltd | Selective somatostatin receptor agonists |
| IL305248A (en) * | 2021-03-04 | 2023-10-01 | Starget Pharma Ltd | Structurally constrained peptide ligands for the somatostatin-3 receptor, their derivatives, and their uses |
| IT202100032615A1 (it) | 2021-12-24 | 2023-06-24 | Italfarmaco Spa | Uso di un agonista della somatostatina nel trattamento di tumori che esprimono SSTR3 |
| CN119708199A (zh) * | 2023-09-27 | 2025-03-28 | 钱杭江医药科技(嘉兴)有限公司 | 生长抑素肽类类似物、螯合物及其应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997001579A2 (en) * | 1995-06-29 | 1997-01-16 | Novartis Ag | Somatostatin peptides |
| EP1598366A1 (en) * | 2004-03-10 | 2005-11-23 | GIUNTINI, Mauro | Somatostatin analogues |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0018891D0 (en) * | 2000-08-01 | 2000-09-20 | Novartis Ag | Organic compounds |
| US6365380B2 (en) | 2000-02-23 | 2002-04-02 | Pcbu Services, Inc. | Method for stereoselectively inverting a chiral center of a chemical compound using an enzyme and a metal catalyst |
| CA2476324A1 (en) * | 2002-03-12 | 2003-09-25 | The Procter & Gamble Company | Cosmetic composition comprising double coated pigment and a gelling agent |
| GB0206415D0 (en) | 2002-03-19 | 2002-05-01 | Glaxo Group Ltd | Deracemisation of amines |
| GB0300095D0 (en) * | 2003-01-03 | 2003-02-05 | Novartis Ag | Organic compounds |
| AR044852A1 (es) * | 2003-06-24 | 2005-10-05 | Novartis Ag | Una composicion farmaceutica para la administracion parenteral que comprende un analogo de somatostatina |
| WO2005013958A1 (en) * | 2003-08-07 | 2005-02-17 | Novartis Ag | Histone deacetylase inhibitors as immunosuppressants |
| GB0318682D0 (en) | 2003-08-08 | 2003-09-10 | Novartis Ag | Organic compounds |
| EP1522311A1 (fr) * | 2003-10-10 | 2005-04-13 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Utilisation de la somatostine ou d'un de ses analogues pour préparer un médicament destiné à réguler la réserve folliculaire ovarienne chez la femme non ménopausée |
| US20070275382A1 (en) * | 2003-11-25 | 2007-11-29 | Muriel Saulnier | Biomarkers for the Efficacy of Somatostatin Analogue Treatment |
| GB0428151D0 (en) | 2004-12-22 | 2005-01-26 | Novartis Ag | Organic compounds |
| US7824663B2 (en) * | 2005-03-10 | 2010-11-02 | Kokyu Alcohol Kogyo Co., Ltd. | Lip gloss composition |
| EP1787658B1 (en) * | 2005-11-10 | 2012-03-14 | CHEMI S.p.A. | Sustained release formulations of somatostatin analogue inhibitors of growth hormone |
| PL2225271T3 (pl) * | 2007-12-03 | 2013-12-31 | Italfarmaco Spa | Nowe nieselektywne analogi somatostatyny |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997001579A2 (en) * | 1995-06-29 | 1997-01-16 | Novartis Ag | Somatostatin peptides |
| EP1598366A1 (en) * | 2004-03-10 | 2005-11-23 | GIUNTINI, Mauro | Somatostatin analogues |
Non-Patent Citations (2)
| Title |
|---|
| Lung Cancer Vol.50(3):319-328 (2005. 12. 01.) * |
| New Journal of Chemistry Vol.27(2):251-256 (2003) * |
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| DK2225271T3 (da) | 2013-10-07 |
| KR20100103464A (ko) | 2010-09-27 |
| BRPI0818978B1 (pt) | 2019-09-10 |
| CA2702940A1 (en) | 2009-06-11 |
| WO2009071460A3 (en) | 2009-12-17 |
| CY1114490T1 (el) | 2016-10-05 |
| US20100323964A1 (en) | 2010-12-23 |
| HRP20130948T1 (hr) | 2013-11-08 |
| SI2225271T1 (sl) | 2013-10-30 |
| US8937152B2 (en) | 2015-01-20 |
| JP5331817B2 (ja) | 2013-10-30 |
| CN101883785B (zh) | 2014-01-15 |
| JP2011505345A (ja) | 2011-02-24 |
| PT2225271E (pt) | 2013-09-27 |
| BRPI0818978B8 (pt) | 2021-05-25 |
| BRPI0818978A2 (pt) | 2016-05-03 |
| WO2009071460A2 (en) | 2009-06-11 |
| CN101883785A (zh) | 2010-11-10 |
| PL2225271T3 (pl) | 2013-12-31 |
| EP2225271A2 (en) | 2010-09-08 |
| CA2702940C (en) | 2016-09-13 |
| EP2225271B1 (en) | 2013-07-31 |
| ES2431573T3 (es) | 2013-11-27 |
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