AU2002348749B2 - Intermediates for LHRH antagonist synthesis, process for their production, and process for LHRH antagonist production - Google Patents
Intermediates for LHRH antagonist synthesis, process for their production, and process for LHRH antagonist production Download PDFInfo
- Publication number
- AU2002348749B2 AU2002348749B2 AU2002348749A AU2002348749A AU2002348749B2 AU 2002348749 B2 AU2002348749 B2 AU 2002348749B2 AU 2002348749 A AU2002348749 A AU 2002348749A AU 2002348749 A AU2002348749 A AU 2002348749A AU 2002348749 B2 AU2002348749 B2 AU 2002348749B2
- Authority
- AU
- Australia
- Prior art keywords
- boc
- heptapeptide
- 4clphe
- 3pal
- lys
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 238000000034 method Methods 0.000 title claims description 29
- 230000008569 process Effects 0.000 title claims description 27
- 229940124041 Luteinizing hormone releasing hormone (LHRH) antagonist Drugs 0.000 title claims description 21
- 239000002474 gonadorelin antagonist Substances 0.000 title claims description 15
- 238000004519 manufacturing process Methods 0.000 title abstract description 10
- 230000015572 biosynthetic process Effects 0.000 title description 13
- 238000003786 synthesis reaction Methods 0.000 title description 11
- 239000000543 intermediate Substances 0.000 title description 9
- 150000003839 salts Chemical class 0.000 claims abstract 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 21
- 150000001413 amino acids Chemical class 0.000 claims description 20
- 125000006239 protecting group Chemical group 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 9
- 238000010511 deprotection reaction Methods 0.000 claims description 9
- VIHYIVKEECZGOU-UHFFFAOYSA-N N-acetylimidazole Chemical compound CC(=O)N1C=CN=C1 VIHYIVKEECZGOU-UHFFFAOYSA-N 0.000 claims description 7
- 230000008878 coupling Effects 0.000 claims description 7
- 238000010168 coupling process Methods 0.000 claims description 7
- 238000005859 coupling reaction Methods 0.000 claims description 7
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 6
- -1 Boc group Chemical group 0.000 claims description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- 108010034529 leucyl-lysine Proteins 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims 1
- 238000006386 neutralization reaction Methods 0.000 claims 1
- URKWHOVNPHQQTM-OAHLLOKOSA-N (2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-naphthalen-2-ylpropanoic acid Chemical compound C1=CC=CC2=CC(C[C@@H](NC(=O)OC(C)(C)C)C(O)=O)=CC=C21 URKWHOVNPHQQTM-OAHLLOKOSA-N 0.000 abstract description 3
- 239000000203 mixture Substances 0.000 description 29
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 18
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 16
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 238000001556 precipitation Methods 0.000 description 6
- 230000021736 acetylation Effects 0.000 description 5
- 238000006640 acetylation reaction Methods 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 229960004592 isopropanol Drugs 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 238000010791 quenching Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 3
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 3
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 229940028334 follicle stimulating hormone Drugs 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- 101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 description 2
- 102100024028 Progonadoliberin-1 Human genes 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- 208000005171 Dysmenorrhea Diseases 0.000 description 1
- 206010013935 Dysmenorrhoea Diseases 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 108700012941 GNRH1 Proteins 0.000 description 1
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 1
- OTXBNHIUIHNGAO-UWVGGRQHSA-N Leu-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(O)=O)CCCCN OTXBNHIUIHNGAO-UWVGGRQHSA-N 0.000 description 1
- 102000009151 Luteinizing Hormone Human genes 0.000 description 1
- 108010073521 Luteinizing Hormone Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010931 ester hydrolysis Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 229940040129 luteinizing hormone Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/23—Luteinising hormone-releasing hormone [LHRH]; Related peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/02—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length in solution
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0827—Tripeptides containing heteroatoms different from O, S, or N
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Analytical Chemistry (AREA)
- Endocrinology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0104463A SE0104463D0 (sv) | 2001-12-29 | 2001-12-29 | Mellanprodukter för syntes af LHRH-antagonister, sätt att framställa dem och sätt för framställning av LHRH-antagonister |
| SE0104463-5 | 2001-12-29 | ||
| PCT/IB2002/005583 WO2003055902A1 (en) | 2001-12-29 | 2002-12-23 | Intermediates for lhrh antagonist synthesis, process for their production, and process for lhrh antagonist production |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2002348749A1 AU2002348749A1 (en) | 2003-07-15 |
| AU2002348749B2 true AU2002348749B2 (en) | 2008-09-04 |
Family
ID=20286557
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2002348749A Ceased AU2002348749B2 (en) | 2001-12-29 | 2002-12-23 | Intermediates for LHRH antagonist synthesis, process for their production, and process for LHRH antagonist production |
Country Status (21)
| Country | Link |
|---|---|
| US (2) | US20050124788A1 (enExample) |
| EP (2) | EP1465917B1 (enExample) |
| JP (1) | JP4272529B2 (enExample) |
| KR (1) | KR100844520B1 (enExample) |
| CN (1) | CN1304417C (enExample) |
| AT (2) | ATE342913T1 (enExample) |
| AU (1) | AU2002348749B2 (enExample) |
| CA (1) | CA2471723C (enExample) |
| CY (2) | CY1107580T1 (enExample) |
| DE (2) | DE60222189T2 (enExample) |
| DK (2) | DK1465917T3 (enExample) |
| ES (2) | ES2296050T3 (enExample) |
| IL (2) | IL162788A0 (enExample) |
| NO (1) | NO330129B1 (enExample) |
| NZ (1) | NZ534245A (enExample) |
| PT (2) | PT1465917E (enExample) |
| RU (1) | RU2307125C2 (enExample) |
| SE (1) | SE0104463D0 (enExample) |
| SI (1) | SI1630169T1 (enExample) |
| WO (1) | WO2003055902A1 (enExample) |
| ZA (1) | ZA200405136B (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4407322B2 (ja) | 2004-03-09 | 2010-02-03 | 味の素株式会社 | ペプチドの製造方法 |
| CN101037472B (zh) * | 2006-03-14 | 2013-03-27 | 中国人民解放军军事医学科学院毒物药物研究所 | 具有低组胺释放作用的促黄体生成素释放激素拮抗剂 |
| TWI442932B (zh) | 2008-02-11 | 2014-07-01 | Ferring Int Ct Sa | 以ＧｎＲＨ拮抗劑治療攝護腺癌的方法 |
| HRP20161746T1 (hr) | 2010-10-27 | 2017-02-10 | Ferring B.V. | Postupak za proizvodnju degareliksa i njegovih međuprodukata |
| EP2447276A1 (en) * | 2010-10-27 | 2012-05-02 | Ferring B.V. | Process for the manufacture of Degarelix and its intermediates |
| FI4512390T1 (fi) | 2012-06-01 | 2025-08-01 | Ferring Bv | Degareliksin valmistaminen |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5710246A (en) * | 1996-03-19 | 1998-01-20 | Abbott Laboratories | Process for intermediates for the synthesis of LHRH antagonists |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4098777A (en) * | 1977-03-14 | 1978-07-04 | Merck & Co., Inc. | Process for the preparation of pyroglutamyl-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn |
| SU1623166A1 (ru) * | 1989-04-03 | 1994-02-15 | Институт биоорганической химии АН БССР | Нейтропептиды, обладающие поведенческой активностью |
| US5225598A (en) * | 1990-03-30 | 1993-07-06 | Union Carbide Chemicals & Plastics Technology Corporation | Selective production of linear pentaethylenehexamine and hydroxyethyldiethylenetriamine |
| CA2086416A1 (en) * | 1990-07-24 | 1992-01-25 | John C. Hubbs | Process for synthesizing peptides |
| AU4394897A (en) * | 1996-10-30 | 1998-05-22 | Pfizer Inc. | Pyridone-fused azabicyclic- or cytisine derivatives, their preparation and the ir use in addiction therapy |
| US5968895A (en) * | 1996-12-11 | 1999-10-19 | Praecis Pharmaceuticals, Inc. | Pharmaceutical formulations for sustained drug delivery |
| DE19941248A1 (de) | 1998-09-01 | 2000-03-02 | Asta Medica Ag | Peptide mit N-substituierten Glycingruppen sowie diese enthaltende Arzneimittel zur Behandlung hormonabhängiger Tumore |
-
2001
- 2001-12-29 SE SE0104463A patent/SE0104463D0/xx unknown
-
2002
- 2002-12-23 EP EP02781699A patent/EP1465917B1/en not_active Expired - Lifetime
- 2002-12-23 SI SI200230642T patent/SI1630169T1/sl unknown
- 2002-12-23 PT PT02781699T patent/PT1465917E/pt unknown
- 2002-12-23 CA CA2471723A patent/CA2471723C/en not_active Expired - Fee Related
- 2002-12-23 CN CNB028283813A patent/CN1304417C/zh not_active Expired - Fee Related
- 2002-12-23 DK DK02781699T patent/DK1465917T3/da active
- 2002-12-23 NZ NZ534245A patent/NZ534245A/en not_active IP Right Cessation
- 2002-12-23 DK DK05025717T patent/DK1630169T3/da active
- 2002-12-23 AT AT02781699T patent/ATE342913T1/de active
- 2002-12-23 DE DE60222189T patent/DE60222189T2/de not_active Expired - Lifetime
- 2002-12-23 DE DE60215544T patent/DE60215544T2/de not_active Expired - Lifetime
- 2002-12-23 RU RU2004119964/04A patent/RU2307125C2/ru not_active IP Right Cessation
- 2002-12-23 AU AU2002348749A patent/AU2002348749B2/en not_active Ceased
- 2002-12-23 US US10/500,047 patent/US20050124788A1/en not_active Abandoned
- 2002-12-23 IL IL16278802A patent/IL162788A0/xx unknown
- 2002-12-23 JP JP2003556432A patent/JP4272529B2/ja not_active Expired - Fee Related
- 2002-12-23 ES ES05025717T patent/ES2296050T3/es not_active Expired - Lifetime
- 2002-12-23 WO PCT/IB2002/005583 patent/WO2003055902A1/en not_active Ceased
- 2002-12-23 ES ES02781699T patent/ES2275012T3/es not_active Expired - Lifetime
- 2002-12-23 PT PT05025717T patent/PT1630169E/pt unknown
- 2002-12-23 EP EP05025717A patent/EP1630169B1/en not_active Expired - Lifetime
- 2002-12-23 AT AT05025717T patent/ATE371666T1/de active
- 2002-12-23 KR KR1020047010267A patent/KR100844520B1/ko not_active Expired - Fee Related
-
2004
- 2004-06-28 ZA ZA2004/05136A patent/ZA200405136B/en unknown
- 2004-06-29 IL IL162788A patent/IL162788A/en not_active IP Right Cessation
- 2004-07-16 NO NO20043047A patent/NO330129B1/no not_active IP Right Cessation
-
2007
- 2007-01-18 CY CY20071100070T patent/CY1107580T1/el unknown
- 2007-11-27 CY CY20071101513T patent/CY1107025T1/el unknown
-
2008
- 2008-08-12 US US12/189,925 patent/US8173770B2/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5710246A (en) * | 1996-03-19 | 1998-01-20 | Abbott Laboratories | Process for intermediates for the synthesis of LHRH antagonists |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |