GB1535602A - Lhrh peptide derivatives - Google Patents

Lhrh peptide derivatives

Info

Publication number
GB1535602A
GB1535602A GB24273/76A GB2427376A GB1535602A GB 1535602 A GB1535602 A GB 1535602A GB 24273/76 A GB24273/76 A GB 24273/76A GB 2427376 A GB2427376 A GB 2427376A GB 1535602 A GB1535602 A GB 1535602A
Authority
GB
United Kingdom
Prior art keywords
ser
leu
trp
pyroglu
gly
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.)
Expired
Application number
GB24273/76A
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.)
Filing date
Publication date
Priority claimed from US05/586,436 external-priority patent/US4018726A/en
Priority claimed from US05/586,437 external-priority patent/US4010125A/en
Priority claimed from US05/652,945 external-priority patent/US4024121A/en
Application filed by Tulane University filed Critical Tulane University
Publication of GB1535602A publication Critical patent/GB1535602A/en
Expired legal-status Critical Current

Links

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

Abstract

1535602 LHRH peptides ADMINISTRATORS OF THE TULANE UNIVERSITY EDUCATIONAL FUND 11 June 1976 [12 June 1975 (2) 27 Jan 1976] 24273/76 Heading C3H Peptides of Formula (I) wherein (i) X is Ser, Y is D-Trp, Z is Gly-NH 2 ; or (ii) X is Ser, Y is D-Phe, Z is Gly-NH 2 ; or (iii) X is D-Ser, Y is D-Leu, Z is NHR<SP>1</SP> wherein R<SP>1</SP> is C 1 -C 3 alkyl; and the non-toxic, pharmaceutically-acceptable salts thereof. The salt may be an acid addition salt, preferably of acetic acid, lactic acid, succinic acid, benzoic acid, salicylic acid, methanesulphonic acid, p - toluenesulphonic acid, hydrochloric acid, phosphoric acid, tannic acid or carboxymethylcellulose. Peptides of Formula (II) wherein (i) X<SP>1</SP> is Ser(R<SP>6</SP>), Y is D-Trp, Z<SP>1</SP> is Gly-R<SP>2</SP>; or (ii) X<SP>1</SP> is Ser(R<SP>6</SP>), Y is D-Phe, Z<SP>1</SP> is Gly-R<SP>2</SP>; or (iii) X<SP>1</SP> is D-Ser(R<SP>6</SP>), Y is D-Leu, Z<SP>1</SP> is OR<SP>3</SP> wherein R<SP>2</SP> is amino or O(C 1 -C 3 alkyl), R<SP>3</SP> is C 1 -C 3 alkyl, R<SP>4</SP>, R<SP>5</SP>, R<SP>6</SP>, R<SP>7</SP> are protective groups which may be eliminated without affecting the compounds of Formula (I), R<SP>8</SP> is hydrogen or one of said protective groups. Peptides of Formula (III) R<SP>8</SP>-Pyroglu-His-Trp-D-Ser(R<SP>6</SP>)-Tyr(R<SP>5</SP>)-D-Leu- Leu-Arg(R<SP>4</SP>)-Pro-NHR<SP>1</SP> wherein R<SP>1</SP> is C 1 -C 3 alkyl. Peptides of Formula (IV) R<SP>8</SP>-Pyroglu-His(R<SP>7</SP>)-Trp-X<SP>1</SP>-Tyr(R<SP>5</SP>)-Y-Leu- Arg(R<SP>4</SP>)-Pro-Z<SP>2</SP> wherein (i) X<SP>1</SP> is Ser(R<SP>6</SP>), Y is D-Trp, Z<SP>2</SP> is Gly-A; or (ii) X<SP>1</SP> is Ser(R<SP>6</SP>), Y is D-Phe, Z<SP>2</SP> is Gly-A; or (iii) X<SP>1</SP> is D-Ser(R<SP>6</SP>), Y is D-Leu, Z<SP>2</SP> is A<SP>1</SP> wherein A is A<SP>1</SP> is (Formula II as shown above) wherein # is phenyl and #<SP>1</SP> is phenylene, R<SP>4</SP> is preferably tosyl, nitro, benzyloxycarbonyl or adamantyloxycarbonyl wherein, if R<SP>4</SP> is nitro or tosyl, protection is on one of the N<SP>#</SP>,N<SP>#1</SP>nitrogen atoms and, if R<SP>4</SP> is benzyloxycarbonyl or adamantyloxycarbonyl, protection is on the N nitrogen atom and one of the N<SP>#</SP>,N<SP>#1</SP>- nitrogen atoms; R<SP>5</SP> is preferably benzyl, 2. bromobenzyloxycarbonyl, acetyl, tosyl, benzoyl, t-butyl, tetrahydropyran-2-yl, trityl, 2,4- dichlorobenzyl or benzyloxycarbonyl; R<SP>7</SP> is preferably tosyl or 2,4-dinitrophenyl; R<SP>8</SP> is preferably t-butyloxycarbonyl, benzyloxycarbonyl, t-amyloxycarbonyl, cyclopentyloxycarbonyl or isobornyloxycarbonyl; R<SP>6</SP> is preferably benzyl, 2-bromobenzyloxycarbonyl, acetyl, tosyl, benzoyl, t-butyl, tetrahydropyran-2-yl, 2,4-dichlorobenzyl, trityl or benzyloxycarbonyl. The peptides may be prepared by solid phase synthesis, preferably using chloromethylated, hydroxymethyl or benzhydrylamine resin. In the examples peptides prepared are: H - Pyroglu - His - Trp - Ser - Tyr - D - Trp- Leu - Arg - Pro - Gly - NH 2 ; H - Pyroglu - His- Trp - Ser - Tyr - D - Phe - Leu - Arg - Pro - Gly- NH 2 ; H - Pyroglu - His - Trp - D - Ser - DLeu - Leu - Arg - Pro - NHC 2 H 5 ; H - Pyroglu- His(Tos) - Ser(Bzl) - Tyr(2BrCbz) - D - Trp- Leu - Arg(Tos) - Pro - Gly - benzhydrylamine resin; H - Pyroglu - His(Tos) - Ser(Bzl) - Tyr- (2BrCbz) - D - Phe - Leu - Arg(Tos) - Pro - Glybenzhydrylamine resin; H - Pyroglu - His- (Dnp) - Trp - D - Ser(Bzl) - Tyr(2BrCbz) - DLeu - Leu - Arg(Tos) - Pro - OCH2 - resin support; H - Pyroglu - His - Trp - D - Ser(Bzl)- Tyr(2BrCbz) - D - Leu - Leu - Arg(Tos) - Pro- NHC 2 H 5 . Pharmaceutical compositions, which may be used to inhibit fertility in female mammals, preferably in unit doage form, comprise peptides (I), or a pharmaceutically-acceptable, non-toxic salt thereof, in admixture with a pharmaceutically-acceptable carrier.
GB24273/76A 1975-06-12 1976-06-11 Lhrh peptide derivatives Expired GB1535602A (en)

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
GB1535602A true GB1535602A (en) 1978-12-13

Family

ID=27416479

Family Applications (1)

Application Number Title Priority Date Filing Date
GB24273/76A Expired GB1535602A (en) 1975-06-12 1976-06-11 Lhrh peptide derivatives

Country Status (11)

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

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2237571A (en) * 1989-11-01 1991-05-08 Robert Peter Millar Gonadotropin releasing hormone analogues

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2450109B1 (en) * 1977-11-08 1986-03-28 Roussel Uclaf NOVEL TREATMENT METHOD USING LH-RH, OR AGONISTS
DE2905502C2 (en) * 1979-02-14 1982-07-15 Hoechst Ag, 6000 Frankfurt Process for the production of LH-RH or LH-RH analogues and pyroglutamyl-N → i → m → -dinitrophenyl-histidine
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 (en) * 1982-02-19 1983-08-26 名伸電機株式会社 Gasket for integrated electricity meter
FI832053L (en) * 1982-06-10 1983-12-11 Syntex Inc NONAPEPTID- OCH DEKAPEPTIDANALOGER AV LHRH ANVAENDBARA SOM LHRH-ANTAGONISTER SAMT DERAS FRAMSTAELLNINGSFOERFARANDE
CH661206A5 (en) * 1983-09-23 1987-07-15 Debiopharm Sa PROCESS FOR THE PREPARATION OF A MEDICINAL PRODUCT FOR THE TREATMENT OF HORMONDEPENDENT DISEASES.
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
DE4342092B4 (en) * 1993-12-09 2007-01-11 Zentaris Gmbh Long-acting suspension for injection and method of preparation
FR2713933B1 (en) * 1993-12-16 1996-02-02 Rhone Merieux Superovulation method for bovine females, anestrus method and appropriate kit.
CA2192782C (en) 1995-12-15 2008-10-14 Nobuyuki Takechi Production of microspheres
CA2192773C (en) 1995-12-15 2008-09-23 Hiroaki Okada Production of sustained-release preparation for injection
WO2003041739A1 (en) 2001-11-13 2003-05-22 Takeda Chemical Industries, Ltd. Anticaner agents

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

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2237571A (en) * 1989-11-01 1991-05-08 Robert Peter Millar Gonadotropin releasing hormone analogues
GB2237571B (en) * 1989-11-01 1993-10-20 Robert Peter Millar Analogues of gonadotropin releasing hormone

Also Published As

Publication number Publication date
NZ181036A (en) 1978-12-18
FR2313940B1 (en) 1979-04-20
JPS6022720B2 (en) 1985-06-03
SE427031B (en) 1983-02-28
SE7606692L (en) 1976-12-13
DE2625843C2 (en) 1985-03-28
JPS5231073A (en) 1977-03-09
CH615662A5 (en) 1980-02-15
AU500087B2 (en) 1979-05-10
CA1067487A (en) 1979-12-04
BE842857A (en) 1976-12-13
HK61079A (en) 1979-09-07
AU1452476A (en) 1977-12-08
FR2313940A1 (en) 1977-01-07
CA1065859A (en) 1979-11-06
DE2625843A1 (en) 1976-12-23

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Legal Events

Date Code Title Description
PS Patent sealed [section 19, patents act 1949]
704A Declaration that licence is not available as of right for an excepted use (par. 4a/1977)
CTFF Supplementary protection certificate filed

Free format text: SPC/GB95/014, 950616

CTFG Supplementary protection certificate granted

Free format text: SPC/GB94/014, 951013, EXPIRES:20010304

CTFG Supplementary protection certificate granted

Free format text: SPC/GB95/014, 951013, EXPIRES:20010304

PE20 Patent expired after termination of 20 years

Effective date: 19960610

CTFE Supplementary protection certificate entered into force

Free format text: SPC/GB95/014, 960611, EXPIRES:20010304

SPCE Supplementary protection certificate expired

Free format text: SPC/GB95/014: 20010304