CA1065859A - Analogues lh-rh et produits intermediaires - Google Patents

Analogues lh-rh et produits intermediaires

Info

Publication number: CA1065859A
Authority: CA; Canada
Prior art keywords: formula; trp; compound; leu; ser
Prior art date: 1975-06-12
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.): Expired

Application number

CA254,039A

Other languages

English (en)

Inventor

Andrew V. Schally

David H. Coy

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Tulane University

Original Assignee

Tulane University

Priority date (The priority date 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 date listed.)

1975-06-12

Filing date

1976-06-04

Publication date

1979-11-06

1975-06-12 Priority claimed from US05/586,436 external-priority patent/US4018726A/en

1975-06-12 Priority claimed from US05/586,437 external-priority patent/US4010125A/en

1976-01-27 Priority claimed from US05/652,945 external-priority patent/US4024121A/en

1976-06-04 Application filed by Tulane University filed Critical Tulane University

1979-11-06 Application granted granted Critical

1979-11-06 Publication of CA1065859A publication Critical patent/CA1065859A/fr

Status Expired legal-status Critical Current

Links

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Classifications

- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S930/00—Peptide or protein sequence
- Y10S930/01—Peptide or protein sequence
- Y10S930/13—Luteinizing hormone-releasing hormone; related peptides
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S930/00—Peptide or protein sequence
- Y10S930/01—Peptide or protein sequence
- Y10S930/28—Bound to a nonpeptide drug, nonpeptide label, nonpeptide carrier, or a nonpeptide resin

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Life Sciences & Earth Sciences (AREA)
Genetics & Genomics (AREA)
Medicinal Chemistry (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Endocrinology (AREA)
Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

CA254,039A 1975-06-12 1976-06-04 Analogues lh-rh et produits intermediaires Expired CA1065859A (fr)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US05/586,436 US4018726A (en)	1975-06-12	1975-06-12	[D-Phe6 ]-LH-RH and intermediates therefor
US05/586,437 US4010125A (en)	1975-06-12	1975-06-12	[D-Trp6 ]-LH-RH and intermediates therefor
US05/652,945 US4024121A (en)	1976-01-27	1976-01-27	(Pyro)-Glu-His-Trp-D-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHR and intermediates

Publications (1)

Publication Number	Publication Date
CA1065859A true CA1065859A (fr)	1979-11-06

Family

ID=27416479

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
CA254,039A Expired CA1065859A (fr)	1975-06-12	1976-06-04	Analogues lh-rh et produits intermediaires
CA 322018 Expired CA1067487A (fr)	1975-06-12	1979-02-21	Analogues de gonadotrophines (lh-rh) et produits intermediaires

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
CA 322018 Expired CA1067487A (fr)	1975-06-12	1979-02-21	Analogues de gonadotrophines (lh-rh) et produits intermediaires

Country Status (11)

Country	Link
JP (1)	JPS6022720B2 (fr)
AU (1)	AU500087B2 (fr)
BE (1)	BE842857A (fr)
CA (2)	CA1065859A (fr)
CH (1)	CH615662A5 (fr)
DE (1)	DE2625843C2 (fr)
FR (1)	FR2313940A1 (fr)
GB (1)	GB1535602A (fr)
HK (1)	HK61079A (fr)
NZ (1)	NZ181036A (fr)
SE (1)	SE427031B (fr)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2450109B1 (fr) *	1977-11-08	1986-03-28	Roussel Uclaf	Nouvelle methode de traitement utilisant la lh-rh, ou des agonistes
DE2905502C2 (de) *	1979-02-14	1982-07-15	Hoechst Ag, 6000 Frankfurt	Verfahren zur Herstellung von LH-RH bzw. LH-RH-Analoga und Pyroglutamyl-N↑i↑m↑-dinitrophenyl-histidin
US4234571A (en) *	1979-06-11	1980-11-18	Syntex (U.S.A.) Inc.	Nonapeptide and decapeptide derivatives of luteinizing hormone releasing hormone
PH19942A (en) *	1980-11-18	1986-08-14	Sintex Inc	Microencapsulation of water soluble polypeptides
IE52535B1 (en) *	1981-02-16	1987-12-09	Ici Plc	Continuous release pharmaceutical compositions
JPS58125819U (ja) *	1982-02-19	1983-08-26	名伸電機株式会社	積算電力量計用パツキン
FI832053A7 (fi) *	1982-06-10	1983-12-11	Syntex Inc	LHRH-antagonistina käyttökelpoinen LHRH:n nonapeptidi- ja dekapeptidianalogit sekä niiden valmistusmenetevalmistusmenetelmä.
CH661206A5 (fr) *	1983-09-23	1987-07-15	Debiopharm Sa	Procede pour la preparation d'un medicament destine au traitement de maladies hormonodependantes.
HU193093B (en) *	1985-04-16	1987-08-28	Innofinance	Process for stimulating sexual activity of birds and domestic mammalians and process for producing spermatocytes for their propagation
CA2029018A1 (fr) *	1989-11-01	1991-05-02	Robert P. Millar	Analogues de l'hormone liberant de la gonadotrophine
DE4342092B4 (de) *	1993-12-09	2007-01-11	Zentaris Gmbh	Langwirkende Injektionssuspension und Verfahren zur Herstellung
FR2713933B1 (fr) *	1993-12-16	1996-02-02	Rhone Merieux	Méthode de superovulation des femelles bovines, méthode de mise en anoestrus et kit approprié.
CA2192773C (fr)	1995-12-15	2008-09-23	Hiroaki Okada	Obtention d'une preparation a liberation prolongee pour injection
CA2192782C (fr)	1995-12-15	2008-10-14	Nobuyuki Takechi	Production de microsphere
EP1444988A4 (fr)	2001-11-13	2007-04-25	Takeda Pharmaceutical	Agents anticancer

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS5726506A (en) *	1980-07-25	1982-02-12	Iseki Agricult Mach	Nursery plant transplanter

1976
- 1976-06-01 NZ NZ181036A patent/NZ181036A/xx unknown
- 1976-06-02 AU AU14524/76A patent/AU500087B2/en not_active Expired
- 1976-06-04 CA CA254,039A patent/CA1065859A/fr not_active Expired
- 1976-06-09 DE DE2625843A patent/DE2625843C2/de not_active Expired
- 1976-06-11 FR FR7617854A patent/FR2313940A1/fr active Granted
- 1976-06-11 SE SE7606692A patent/SE427031B/xx active Protection Beyond IP Right Term
- 1976-06-11 JP JP51069247A patent/JPS6022720B2/ja not_active Expired
- 1976-06-11 BE BE167844A patent/BE842857A/fr not_active IP Right Cessation
- 1976-06-11 GB GB24273/76A patent/GB1535602A/en not_active Expired
- 1976-06-11 CH CH747476A patent/CH615662A5/fr not_active IP Right Cessation
1979
- 1979-02-21 CA CA 322018 patent/CA1067487A/fr not_active Expired
- 1979-08-30 HK HK610/79A patent/HK61079A/xx unknown

Also Published As

Publication number	Publication date
CH615662A5 (en)	1980-02-15
NZ181036A (en)	1978-12-18
JPS6022720B2 (ja)	1985-06-03
FR2313940B1 (fr)	1979-04-20
FR2313940A1 (fr)	1977-01-07
DE2625843A1 (de)	1976-12-23
JPS5231073A (en)	1977-03-09
BE842857A (fr)	1976-12-13
HK61079A (en)	1979-09-07
AU500087B2 (en)	1979-05-10
GB1535602A (en)	1978-12-13
SE7606692L (sv)	1976-12-13
SE427031B (sv)	1983-02-28
CA1067487A (fr)	1979-12-04
AU1452476A (en)	1977-12-08
DE2625843C2 (de)	1985-03-28

Publication	Publication Date	Title
US4010125A (en)	1977-03-01	[D-Trp6 ]-LH-RH and intermediates therefor
CA1339043C (fr)	1997-04-01	Analogues nonapeptidiques et decapeptidiques de lhrh, utiles comme antagonistes de lhrh
US4018726A (en)	1977-04-19	[D-Phe6 ]-LH-RH and intermediates therefor
KR0135276B1 (ko)	1998-04-23	무시할 정도의 히스타민을 방출하는 투테인화 호르몬 방출호르몬의 효과있는 길항제
AU675274B2 (en)	1997-01-30	Reduced size LHRH analogs
US4317815A (en)	1982-03-02	LH-RH Antagonists
CA1267999A (fr)	1990-04-17	Nonapeptide et decapeptide analogues de la lh-rh utiles comme agoniste de la lh-rh
US4341767A (en)	1982-07-27	Nonapeptide and decapeptide analogs of LHRH, useful as LHRH antagonists
US4690916A (en)	1987-09-01	Nona and decapeptide analogs of LHRH useful as LHRH antagonists
WO1984002341A1 (fr)	1984-06-21	AGONISTES DE GnRH
US4024121A (en)	1977-05-17	(Pyro)-Glu-His-Trp-D-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHR and intermediates
CA1067487A (fr)	1979-12-04	Analogues de gonadotrophines (lh-rh) et produits intermediaires
US4431635A (en)	1984-02-14	LH-RH Antagonists
US3835108A (en)	1974-09-10	Process for preparing the releasing hormone of luteinizing hormone(lh)and of follicle stimulating hormone(fsh),salts and compositions thereof,and intermediates therefor
EP0081877B1 (fr)	1986-04-30	Antagonistes de LH-RH
US4632979A (en)	1986-12-30	Therapeutic LHRH analogs
EP0041286B1 (fr)	1984-08-15	Antagonistes de la LH-RH
EP0125290B1 (fr)	1989-02-08	Peptides agissant sur la fonction gonadique
EP0673254A1 (fr)	1995-09-27	Antagonistes de l'hormone liberant l'hormone luteinisante (lhrh) de decapeptides modifies en position 6
Kovacs et al.	1984	Long-term inhibition of ovulation by a GnRH-antagonist at low dose level
US5382568A (en)	1995-01-17	Decapeptide having dopamine stimulating activity
CA1074785A (fr)	1980-04-01	Procede de preparation d'un nonapeptide capable de liberer des hormones luteinisante et folliculo-stimulante et produit intermediaire
GB2053229A (en)	1981-02-04	LH-RH antagonists