FI91074B - Förfarande för framställning av terapeutiskt användbar GRF-analog, vilken innehåller en ringstruktur - Google Patents
Förfarande för framställning av terapeutiskt användbar GRF-analog, vilken innehåller en ringstruktur Download PDFInfo
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- FI91074B FI91074B FI893532A FI893532A FI91074B FI 91074 B FI91074 B FI 91074B FI 893532 A FI893532 A FI 893532A FI 893532 A FI893532 A FI 893532A FI 91074 B FI91074 B FI 91074B
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- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
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- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/60—Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Endocrinology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Diabetes (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Amplifiers (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Diaphragms For Electromechanical Transducers (AREA)
- Luminescent Compositions (AREA)
- Control Of El Displays (AREA)
Claims (8)
1. Förfarande för framställning av en terapeutiskt användbar GRF-analog innehctllande 29 - 44 aminosyragrup-5 per, vilken innehäller en ringstruktur me11an aminosyrorna R25 och R29 och vars N-terminala sekvens har formeln I: (BJR^R^Asp-Ala-Ile-Phe-Thr-Rg-Ser-Tyr-Arg-R^-Ru-Leu-Ru- Gln-Leu-Rig-Ala-Arg-Lys-Leu-Leu-R^-R^-Ile-Nle-Rjg-R^- 10 i vilken B är H eller C“Me, R, är Tyr eller His, R2 är Ala eller D-NMA, R8 är Ser, Lys eller Asn, R12 är Arg eller Lys, Ri3 är Ile eller Vai, R,s är Ala eller Gly, R,8 är Tyr eller Ser, R24 är His eller Gin, R2J är Cys, D-Cys, D-Glu eller 15 Asp, R28 är Asn eller Ser och R29 är Cys, D-Cys, Orn eller daP förutsatt, att dä Ry är D-Cys eller Cys, R29 är obe-roende D-Cys eller Cys, och dä R25 är Asp eller D-Glu, R29 är oberoende Orn eller daP, och varvid de eventuellt före-kominande aminosyrorna 30 - 44 eller frän C-terminalen för-20 kortade fragment av sekvensen de bildar motsvarar struktu-ren hos naturligt GRF, samt farmaceutiskt godtagbara sal-ter av denna, kännetecknat därav, att (a) man bildar en peptidmellanprodukt som innehäller ät-minstone en skyddsgrupp och vars N-terminala sekvens har 25 formeln II: (X1) (B)R,(X eller X2)-R2-Asp(X})-Ala-Ile-Phe-Thr(X4)-R8(X\ X5 tai X7) -Ser (X4) -Tyr (X2) -Arg(X*) -R12 (X6 eller X7)-R13-Leu-R15-Gln (X5)-Leu-R18(X2 eller X4)-Ala-Arg (X6)-Lys (X7)-Leu-Leu-R24 (X el-30 ler X5)-R23 (X8)-Ile-Nle-R28 (Xs eller X4)-R29(X8)---X10, II vilka var och en av X, X1, X2, X3, X4, X5, X6 och X7 är väte 2 eller en sedvanlig skyddsgrupp för sidokedjan, X* är en 3 skyddsgrupp för sulfhydrylgruppen i Cys eller en lämplig 91074 skyddsgrupp för aminosidokedjan, vilken grupp kan avlägs-nas utan att samtidigt avlägsna skyddsgruppen X7, eller en lämplig labil skyddsgrupp för karboxylsidokedjan, vilken grupp kan avlägsnas utan att samtidigt avlägsna skydds- 5 gruppen X3, --- anger att andra aminosyror kan föreligga, och X10 är en förankrande bindning tili hartset, (b) skyddsgruppen eller skyddsgrupperna eller den förankrande bindningen avspjälks frän peptidmellanprodukten med formeln II, 10 (c) en cyklisernade bindning bildas mellan grupperna Ry och R29, om en sädan inte föreligger, antingen före eller efter steg (b), och (d) om sä önskas överförs den erhällna peptiden i ett giftfritt sait. 15
2. Förfarande enligt patentkrav l, k ä n n e - t e c k n a t därav, att R, är N*MeTyr.
3. Förfarande enligt patentkrav 1 eller 2, k ä n -netecknat därav, att R2J är D-Cys och R29 är Cys.
4. Förfarande enligt patentkrav l eller 2, k ä n - 20 netecknat därav, att Ry är Asp och R29 är dAP.
5. Förfarande enligt patentkrav 1 eller 2, k ä n -netecknat därav, att Ry är D-Glu och R29 är Orn.
6. Förfarande enligt patentkrav 1 eller 2, k ä n -netecknat därav, att Ry är Cys och R29 är D-Cys. 25
7. Förfarande enligt patentkrav 1, k ä n ne tecknat därav, att peptiden har en av formlerna: [N^MeTyr1, Ala15, D-Cys25, Nle27, Cys29]-rGRF( 1-29)-NH2, [N*MeTyr!, Ala15, Cys25, Nle27, D-Cys29]-rGRF(l-29)-NH2, 30 [N*MeTyr’, Lys8, Ala15, D-Cys25, Nle27, Asn28, Cys29]-hGRF (1-29)-NHEt, [N*MeTyr', D-NMA2, Ala15, Nle27, daP29] -hGRF (1-44) -NH2 och [D-NMA2, D-Glu25, Nle27, Orn29] -rGRF(l-43) -OH.
8. Förfarande enligt patentkrav 4 eller 5, k ä n -netecknat därav, att den cykliserande bindningen bildas genom att avlägsna skyddet frän grupperna R25 och R29 och bilda en amidbindning mellan deras sidokedjor, varvid 5 peptidmellanprodukten förblir bunden tili hartset. li
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/223,277 US5043322A (en) | 1988-07-22 | 1988-07-22 | Cyclic GRF analogs |
| US22327788 | 1988-07-22 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI893532A0 FI893532A0 (sv) | 1989-07-21 |
| FI893532A FI893532A (sv) | 1990-01-23 |
| FI91074B true FI91074B (sv) | 1994-01-31 |
| FI91074C FI91074C (sv) | 1994-05-10 |
Family
ID=22835815
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI893532A FI91074C (sv) | 1988-07-22 | 1989-07-21 | Förfarande för framställning av terapeutiskt användbar GRF-analog, vilken innehåller en ringstruktur |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US5043322A (sv) |
| EP (1) | EP0352014B1 (sv) |
| JP (1) | JP2739910B2 (sv) |
| KR (1) | KR0138907B1 (sv) |
| AT (1) | ATE103609T1 (sv) |
| DE (1) | DE68914205T2 (sv) |
| DK (1) | DK355889A (sv) |
| ES (1) | ES2055792T3 (sv) |
| FI (1) | FI91074C (sv) |
| IE (1) | IE892378L (sv) |
| IL (1) | IL90766A0 (sv) |
| NO (1) | NO892970L (sv) |
| ZA (1) | ZA895050B (sv) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0542937A1 (en) * | 1991-04-09 | 1993-05-26 | F. Hoffmann-La Roche Ag | Growth hormone releasing factor analogs |
| US5262519A (en) * | 1991-05-15 | 1993-11-16 | The Salk Institute For Biological Studies | GRF analogs XI |
| US5371070A (en) * | 1992-11-09 | 1994-12-06 | The Salk Institute For Biological Studies | Bicyclic GnRH antagonists and a method for regulating the secretion of gonadotropins |
| US6008058A (en) * | 1993-06-18 | 1999-12-28 | University Of Louisville | Cyclic peptide mixtures via side chain or backbone attachment and solid phase synthesis |
| US5780220A (en) * | 1994-05-19 | 1998-07-14 | Trustees Of The University Of Pennsylvania | Methods and compositions for inhibiting HIV replication |
| US5639598A (en) * | 1994-05-19 | 1997-06-17 | The Trustees Of The University Of Pennsylvania | Method and kit for identification of antiviral agents capable of abrogating HIV Vpr-Rip-1 binding interactions |
| US5942489A (en) * | 1996-05-03 | 1999-08-24 | The Administrators Of The Tulane Educational Fund | HGH-RH(1-29)NH2 analogues having antagonistic activity |
| US7015309B1 (en) | 1999-06-23 | 2006-03-21 | The Wistar Institute Of Anatomy And Biology | Pyrrhocoricin-derived peptides, and methods of use thereof |
| WO2000078956A1 (en) * | 1999-06-23 | 2000-12-28 | The Wistar Institute Of Anatomy And Biology | Novel pyrrhocoricin-derived peptides, and methods of use thereof |
| WO2008095063A1 (en) | 2007-01-31 | 2008-08-07 | Dana-Farber Cancer Institute, Inc. | Stabilized p53 peptides and uses thereof |
| KR101623985B1 (ko) | 2007-03-28 | 2016-05-25 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 스티칭된 폴리펩티드 |
| RU2582678C2 (ru) | 2010-08-13 | 2016-04-27 | Эйлерон Терапьютикс, Инк. | Пептидомиметические макроциклы |
| EP2654772B1 (en) | 2010-12-22 | 2018-09-26 | The Salk Institute for Biological Studies | Cyclic crf antagonist peptides |
| TWI643868B (zh) * | 2011-10-18 | 2018-12-11 | 艾利倫治療公司 | 擬肽巨環化合物 |
| CA2864120A1 (en) | 2012-02-15 | 2013-08-22 | Aileron Therapeutics, Inc. | Triazole-crosslinked and thioether-crosslinked peptidomimetic macrocycles |
| WO2013123266A1 (en) | 2012-02-15 | 2013-08-22 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| SG11201503052RA (en) | 2012-11-01 | 2015-05-28 | Aileron Therapeutics Inc | Disubstituted amino acids and methods of preparation and use thereof |
| US10471120B2 (en) | 2014-09-24 | 2019-11-12 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| CN107614003A (zh) | 2015-03-20 | 2018-01-19 | 艾瑞朗医疗公司 | 拟肽大环化合物及其用途 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4595676A (en) * | 1983-04-26 | 1986-06-17 | The Salk Institute For Biological Studies | Rat hypothalamic GRF |
| US4563352A (en) * | 1982-10-04 | 1986-01-07 | The Salk Institute For Biological Studies | Human pancreatic GRF |
| US4518586A (en) * | 1983-01-13 | 1985-05-21 | The Salk Institute For Biological Studies | GRF Analogs III |
| US4626523A (en) * | 1983-09-13 | 1986-12-02 | The Salk Institute For Biological Studies | GRF analogs II |
| US4528190A (en) * | 1983-10-25 | 1985-07-09 | The Salk Institute For Biological Studies | GRF Analogs IV |
| US4661472A (en) * | 1985-05-09 | 1987-04-28 | The Salk Institute For Biological Studies | GnRH antagonists IX |
| US4734399A (en) * | 1985-08-06 | 1988-03-29 | Hoffmann-La Roche Inc. | Growth hormone releasing factor analogs |
| US4689318A (en) * | 1985-08-29 | 1987-08-25 | The Salk Institute For Biological Studies | GRF analogs |
| IL84758A (en) * | 1987-01-13 | 1992-03-29 | Salk Inst For Biological Studi | Peptides stimulating the release of pituitary growth hormone in fish and amphibians,and pharmaceutical compositions containing them |
| US4784987A (en) * | 1987-01-13 | 1988-11-15 | The Salk Institute For Biological Studies | GRF analogs VI |
| ATE106895T1 (de) * | 1987-09-18 | 1994-06-15 | Hoffmann La Roche | Zyklische grf-analoga. |
-
1988
- 1988-07-22 US US07/223,277 patent/US5043322A/en not_active Expired - Lifetime
-
1989
- 1989-06-27 IL IL90766A patent/IL90766A0/xx not_active IP Right Cessation
- 1989-07-03 ZA ZA895050A patent/ZA895050B/xx unknown
- 1989-07-13 EP EP89307089A patent/EP0352014B1/en not_active Expired - Lifetime
- 1989-07-13 AT AT89307089T patent/ATE103609T1/de not_active IP Right Cessation
- 1989-07-13 DE DE68914205T patent/DE68914205T2/de not_active Expired - Fee Related
- 1989-07-13 ES ES89307089T patent/ES2055792T3/es not_active Expired - Lifetime
- 1989-07-18 DK DK355889A patent/DK355889A/da not_active Application Discontinuation
- 1989-07-20 NO NO89892970A patent/NO892970L/no unknown
- 1989-07-21 FI FI893532A patent/FI91074C/sv not_active IP Right Cessation
- 1989-07-21 IE IE892378A patent/IE892378L/xx unknown
- 1989-07-21 KR KR1019890010373A patent/KR0138907B1/ko not_active IP Right Cessation
- 1989-07-24 JP JP1191231A patent/JP2739910B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| KR0138907B1 (ko) | 1998-04-30 |
| EP0352014A2 (en) | 1990-01-24 |
| ES2055792T3 (es) | 1994-09-01 |
| ATE103609T1 (de) | 1994-04-15 |
| ZA895050B (en) | 1990-04-25 |
| DE68914205T2 (de) | 1994-07-07 |
| IE892378L (en) | 1990-01-22 |
| JPH0269499A (ja) | 1990-03-08 |
| NO892970D0 (no) | 1989-07-20 |
| KR910002900A (ko) | 1991-02-26 |
| EP0352014B1 (en) | 1994-03-30 |
| JP2739910B2 (ja) | 1998-04-15 |
| FI893532A (sv) | 1990-01-23 |
| FI91074C (sv) | 1994-05-10 |
| DE68914205D1 (de) | 1994-05-05 |
| EP0352014A3 (en) | 1991-07-03 |
| IL90766A0 (en) | 1990-01-18 |
| DK355889D0 (da) | 1989-07-18 |
| DK355889A (da) | 1990-01-23 |
| US5043322A (en) | 1991-08-27 |
| FI893532A0 (sv) | 1989-07-21 |
| NO892970L (no) | 1990-01-23 |
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Owner name: THE SALK INSTITUTE FOR BIOLOGICAL |