SE7606692L - LH-RH ANALOGS AND INTERMEDIATE PRODUCTS - Google Patents

LH-RH ANALOGS AND INTERMEDIATE PRODUCTS

Info

Publication number
SE7606692L
SE7606692L SE7606692A SE7606692A SE7606692L SE 7606692 L SE7606692 L SE 7606692L SE 7606692 A SE7606692 A SE 7606692A SE 7606692 A SE7606692 A SE 7606692A SE 7606692 L SE7606692 L SE 7606692L
Authority
SE
Sweden
Prior art keywords
ser
leu
trp
pyroglu
gly
Prior art date
Application number
SE7606692A
Other languages
Unknown language ( )
Swedish (sv)
Other versions
SE427031B (en
Inventor
Andrew Victor Schally
David Howard Coy
Original Assignee
Andrew Victor Schally
David Howard Coy
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 Andrew Victor Schally, David Howard Coy filed Critical Andrew Victor Schally
Publication of SE7606692L publication Critical patent/SE7606692L/en
Publication of SE427031B publication Critical patent/SE427031B/en

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.
SE7606692A 1975-06-12 1976-06-11 PROCEDURE FOR THE PREPARATION OF (D-TRP? 726) -LH-RH SE427031B (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 (2)

Publication Number Publication Date
SE7606692L true SE7606692L (en) 1976-12-13
SE427031B SE427031B (en) 1983-02-28

Family

ID=27416479

Family Applications (1)

Application Number Title Priority Date Filing Date
SE7606692A SE427031B (en) 1975-06-12 1976-06-11 PROCEDURE FOR THE PREPARATION OF (D-TRP? 726) -LH-RH

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)

Families Citing this family (15)

* 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
CA2029018A1 (en) * 1989-11-01 1991-05-02 Robert P. Millar Analogues of gonadotropin releasing hormone
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.
CA2192773C (en) 1995-12-15 2008-09-23 Hiroaki Okada Production of sustained-release preparation for injection
CA2192782C (en) 1995-12-15 2008-10-14 Nobuyuki Takechi Production of microspheres
CA2466659A1 (en) 2001-11-13 2003-05-22 Takeda Chemical Industries, Ltd. Anticancer 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

Also Published As

Publication number Publication date
DE2625843C2 (en) 1985-03-28
CH615662A5 (en) 1980-02-15
SE427031B (en) 1983-02-28
AU500087B2 (en) 1979-05-10
BE842857A (en) 1976-12-13
FR2313940A1 (en) 1977-01-07
GB1535602A (en) 1978-12-13
NZ181036A (en) 1978-12-18
DE2625843A1 (en) 1976-12-23
JPS5231073A (en) 1977-03-09
CA1065859A (en) 1979-11-06
HK61079A (en) 1979-09-07
JPS6022720B2 (en) 1985-06-03
CA1067487A (en) 1979-12-04
AU1452476A (en) 1977-12-08
FR2313940B1 (en) 1979-04-20

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