EP0037246A2
Expired / Lapsed
EP
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Polypeptides
Assignee: Wyeth LLC
•
Filing: 1981-03-25
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Granted: —
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Expires: 2001-03-25
Abstract
Abstract There are disclosed polypeptides having the following formula: wherein R is hydrogen, alkanoyl of 1-4 carbon atoms or aroyl of 6-10 carbon atoms; X 1 is L-Arg, D-Arg or D-homoarginine; X 3 is Asn, Gin or the N-substituted carboxamides thereof; X 5 is L- or D-Tyr, L- or D-Phe, L- or D-Trp, L- or D-Leu, L- or D-Met, D-Met-ol-oxide or D-Phe-ol; and R 1 is amino, monoalkylamino of 1-4 carbon atoms, dialkylamino wherein each alkyl has 1-4 carbon atoms, hydroxy, alkoxy of 1-4 carbon atoms, the fully protected peptide-resin intermediates thereof, and pharmaceutically acceptable salts thereof. These polypeptides have the capability of inducing the differentiation of T-lymphocytes and thus are useful in a number of therapeutic areas. Processes for preparing the polypeptides are also disclosed.
Inventors
- 👤 Dimitrios Sarantakis
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-09 07:36
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/575; C07K14/66; C07K14/662; A; A61; A61K; A61K38/00; Y; Y10; Y10S; Y10S930/00; Y10S930/01; Y10S930/18; Y10S930/28
Claims Analysis
Total Claims: 29
Claim 1
Independent Claim
99 words
A polypeptide having the following formula: wherein R is hydrogen, alkanoyl of 1 - 4 carbon atoms or aroyl of 6-10 carbon atoms; X 1 is L-Arg, D-Arg or D-homoarginine; X 3 is Asn, Gln or the N-substituted carboxamides thereof; X 5 is L- or D-Tyr, L- or D-Phe, L- or D-Trp, L- or D-Leu, L- or D-Met, D-Met -ol-oxide or D-Phe-ol; and R 1 is amino, monoalkylamino of 1 - 4 carbon atoms, dialkylamino wherein each alkyl has 1-4 carbon atoms, hydroxy, alkoxy of 1-4 carbon atoms, the fully protected peptide-resin intermediates thereof, or pharmaceutically acceptable salts thereof.
Claim 2
Dependent Claim
99 words
A polypeptide having the following formula: wherein R is hydrogen, alkanoyl of 1 - 4 carbon atoms or aroyl of 6-10 carbon atoms; X 1 is L-Arg, D-Arg or D-homoarginine; X 3 is Asn, Gln or the N-substituted carboxamides thereof; X 5 is L- or D-Tyr, L- or D-Phe, L- or D-Trp, L- or D-Leu, L- or D-Met, D-Met -ol-oxide or D-Phe-ol; and R 1 is amino, monoalkylamino of 1 - 4 carbon atoms, dialkylamino wherein each alkyl has 1-4 carbon atoms, hydroxy, alkoxy of 1-4 carbon atoms, the fully protected peptide-resin intermediates thereof, or pharmaceutically acceptable salts thereof.
Claim 3
Dependent Claim
91 words
A polypeptide having the following formula: wherein R is hydrogen, alkanoyl of 1-4 carbon atoms or aroyl of 6-10 carbon atoms; X 1 is L-Arg, D-Arg or D-homoarginine; X 3 is Asn, Gln or the N-substituted carboxamides thereof; X 5 is L- or D-Phe, L- or D-Trp, L- or D-Leu, L- or D-Met, D-Met-ol-oxide or D-Phe-ol; and R 1 is amino, monoalkylamino of 1-4 carbon atoms, dialkylamino wherein each alkyl has 1-4 carbon atoms, hydroxy, alkoxy of 1-4 carbon atoms, the fully protected peptide-resin intermediates thereof, or pharmaceutically acceptable salts thereof.
Claim 4
Dependent Claim
91 words
A polypeptide having the following formula: wherein R is hydrogen, alkanoyl of 1-4 carbon atoms or aroyl of 6-10 carbon atoms; X 1 is L-Arg, D-Arg or D-homoarginine; X 3 is Asn, Gln or the N-substituted carboxamides thereof; X 5 is L- or D-Phe, L- or D-Trp, L- or D-Leu, L- or D-Met, D-Met-ol-oxide or D-Phe-ol; and R 1 is amino, monoalkylamino of 1-4 carbon atoms, dialkylamino wherein each alkyl has 1-4 carbon atoms, hydroxy, alkoxy of 1-4 carbon atoms, the fully protected peptide-resin intermediates thereof, or pharmaceutically acceptable salts thereof.
Claim 5
Dependent Claim
15 words
A compound of Claim 1, which is Arg-Lys-Asn-Val-Tyr-NH 2 or a pharmaceutically acceptable salt thereof.
Claim 6
Dependent Claim
15 words
A compound of Claim 1, which is D-Arg-Lys-Asn-Val-D-Phe-NH 2 or a pharmaceutically acceptable salt thereof.
Claim 7
Dependent Claim
85 words
A compound of the formula: wherein X 1 is L-Arg, D-Arg or D-homoarginine; X 3 is Asn, Gln or the N-substituted carboxamide thereof; X 5 is L- or D-Tyr, L- or D-Phe, L- or D-Trp, L- or D-Leu, L- or D-Met, D-Met-ol-oxide or D-Phe-ol; A is an a-amino protecting group B is a protecting group for the guanyl group of arginine; C is an amino protecting group; and D is a protecting group for the hydroxyl group of tyrosine or the imino group of tryptophan
Claim 8
Dependent Claim
85 words
A compound of the formula: wherein X 1 is L-Arg, D-Arg or D-homoarginine; X 3 is Asn, Gln or the N-substituted carboxamide thereof; X 5 is L- or D-Tyr, L- or D-Phe, L- or D-Trp, L- or D-Leu, L- or D-Met, D-Met-ol-oxide or D-Phe-ol; A is an a-amino protecting group B is a protecting group for the guanyl group of arginine; C is an amino protecting group; and D is a protecting group for the hydroxyl group of tyrosine or the imino group of tryptophan
Claim 9
Dependent Claim
76 words
A compound of the formula: wherein X 1 is L-Arg, D-Arg or D-homoarginine; X 3 is Asn, Gln or the N-substituted carboxamides thereof; X 5 is L- or D-Phe, L- or D-Trp, L- or D-Leu, L- or D-Met, D-Met-ol-oxide or D-Phe-ol; A is an a-amino protecting group B is a protecting group for the guanyl group of arginine; C is an amino protecting group; and D is a protecting group for the imino group of tryptophan.
Claim 10
Dependent Claim
76 words
A compound of the formula: wherein X 1 is L-Arg, D-Arg or D-homoarginine; X 3 is Asn, Gln or the N-substituted carboxamides thereof; X 5 is L- or D-Phe, L- or D-Trp, L- or D-Leu, L- or D-Met, D-Met-ol-oxide or D-Phe-ol; A is an a-amino protecting group B is a protecting group for the guanyl group of arginine; C is an amino protecting group; and D is a protecting group for the imino group of tryptophan.
Claim 11
Dependent Claim
22 words
A compound of Claim 5 having the formula: wherein A is t-butyloxycarbonyl; B is tosyl; C is 2-chlorobenzyloxycarbonyl; and D is 2,6-dichlorobenzyl.
Claim 12
Dependent Claim
19 words
A compound of Claim 5 having the formula: wherein A is t-butyloxycarbonyl; B is tosyl; and C is 2-chlorobenzyloxycarbonyl.
Claim 13
Dependent Claim
27 words
A polypeptide of formula I, as defined in Claim 1, or a pharmaceutically acceptable salt thereof, for use in the treatment of disorders involving an immune response.
Claim 14
Dependent Claim
25 words
A pharmaceutical composition, comprising a peptide of formula I, as defined in Claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
Claim 15
Dependent Claim
43 words
A process for preparing a polypeptide of formula I, as defined in Claim 1, or a pharmaceutically acceptable salt thereof characterised in that a protected intermediate for said polypeptide is deprotected and if desired the product is isolated as a pharmaceutically acceptable salt.
Claim 16
Dependent Claim
49 words
A process as claimed in Claim 11, characterised in that the protected intermediate is a peptide-resin intermediate as defined in any one of claims 1, 2, 5, 6, 7 or 8 and the peptide of formula I is prepared by cleaving the peptide from the resin and deprotecting it.
Claim 17
Dependent Claim
117 words
1 . A process for preparing a polypeptide having the formula wherein R is hydrogen, alkanoyl of 1-4 carbon atoms or aroyl of 6-10 carbon atoms; X 1 is L-Arg, D-Arg or D-homoarginine; X 3 is Asn, Gln or the N-substituted carboxamides thereof; X 5 is L- or D-Tyr, L- or D-Phe, L- or D-Trp, L- or D-Leu, L- or D-Met, D-Met-ol-oxide or D-Phe-ol; and R 1 is amino, monoalkylamino of 1-4 carbon atoms, dialkylamino wherein each alkyl has 1-4 carbon atoms, hydroxy, alkoxy of 1-4 carbon atoms, or a pharmaceutically acceptable salt thereof, characterised in that a protected intermediate for said polypeptide is deprotected and if desired the product is isolated as a pharmaceutically acceptable salt.
Claim 18
Dependent Claim
117 words
1 . A process for preparing a polypeptide having the formula wherein R is hydrogen, alkanoyl of 1-4 carbon atoms or aroyl of 6-10 carbon atoms; X 1 is L-Arg, D-Arg or D-homoarginine; X 3 is Asn, Gln or the N-substituted carboxamides thereof; X 5 is L- or D-Tyr, L- or D-Phe, L- or D-Trp, L- or D-Leu, L- or D-Met, D-Met-ol-oxide or D-Phe-ol; and R 1 is amino, monoalkylamino of 1-4 carbon atoms, dialkylamino wherein each alkyl has 1-4 carbon atoms, hydroxy, alkoxy of 1-4 carbon atoms, or a pharmaceutically acceptable salt thereof, characterised in that a protected intermediate for said polypeptide is deprotected and if desired the product is isolated as a pharmaceutically acceptable salt.
Claim 19
Dependent Claim
39 words
A process as claimed in Claim 1, characterised in that the protected intermediate is a peptide-resin intermediate and the polypeptide of formula I is deprotected and cleaved from the resin, and if desired isolated as a pharmaceutically acceptable salt.
Claim 20
Dependent Claim
55 words
A process for preparing a polypeptide of formula I, or a pharmaceutically acceptable salt thereof, as defined in Claim 1, characterised in that the polypeptide is prepared by condensing the requisite amino acids/amides, protected and/or activated if necessary, to give the desired sequence, deprotecting and if desired isolating the product as a pharmaceutically acceptable salt.
Claim 21
Dependent Claim
80 words
A process for preparing a polypeptide of formula I, or a pharmaceutically acceptable salt thereof, as defined in Claim 1, characterised in that, the poly peptide is prepared by condensing the requisite amino acids/amides, protected and/or activated if necessary under solid phase conditions on a resin support to obtain a peptide-resin intermediate and the polypeptide of formula I is cleaved from the resin and deprotected, and if desired the polypeptide of formula I is isolated as a pharmaceutically acceptable salt.
Claim 22
Dependent Claim
31 words
A process as claimed in any one of the preceding claims characterised in that the peptide of formula I which is prepared is : Arg-Lys-Asn-Val-Tyr-NH2 or a pharmaceutically acceptable salt thereof.
Claim 23
Dependent Claim
29 words
A process as claimed in any one of claims 1-4, characterised in that the peptide of formula I which is oreoared is : or a pharmaceutically acceptable salt thereof.
Claim 24
Dependent Claim
99 words
A process as claimed in Claim 2, characterised in that the peptide resin intermediate is a compound of formula wherein X 1 is L-Arg, D-Arg or D-homoarginine; X 3 is Asn, Gln or the N-substituted carboxamides thereof; X 5 is L- or D-Tyr, L- or D-Phe, L- or D-Trp, L- or D-Leu, L- or D-Met, D-Met-ol-oxide or D-Phe-ol; A is an α-amino protecting group B is a protecting group for the guanyl group of arginine; C is an amino protecting group; and D is a protecting group for the hydroxyl group of tyrosine or the imino group of tryptophan.
Claim 25
Dependent Claim
91 words
A process as claimed in Claim 2 characterised in that the peptide resin intermediate is a compound of the formula: wherein X 1 is L-Arg, D-Arg or D-homoarginine; X 3 is Asn, Gln or the N-substituted carboxamides thereof; X 5 is L- or D-Phe, L- or D-Trp, L- or D-Leu, L- or D-Met, D-Met-ol-oxide or D-Phe-ol; A is an a-amino protecting group B is a protecting group for the guanyl group of arginine; C is an amino protecting group; and D is a protecting group for the imino group of tryptophan.
Claim 26
Dependent Claim
34 words
A process as claimed in Claim 2, characterised in that the peptide resin intermediate is the compound having the formula: wherein A is t-butyloxycarbonyl; B is tosyl; C is 2-chlorobenzyloxycarbonyl; and D is 2,6-dichlorobenzyl.
Claim 27
Dependent Claim
31 words
A process as claimed in Claim 2, characterised in that the peptide resin intermediate is the compound having the formula: wherein A is t-butyloxycarbonyl; B is tosyl; and C is 2-chlorobenzyloxycarbonyl.
Claim 28
Dependent Claim
41 words
A process for preparing a pharmaceutically acceptable salt of a peptide of formula I as defined in Claim 1, characterised in that a peptide of formula I is treated with a pharmaceutically acceptable acid to obtain the corresponding acid addition salt.
Claim 29
Dependent Claim
52 words
A process for preparing a pharmaceutical composition for use in the treatment of disorders involving an immune response, characterised in that a peptide of formula I, as defined in Claim 1, or a pharmaceutically acceptable salt thereof, is mixed with a pharmaceutical carrier and brought into a form suitable for therapeutic administration.
References Cited (Backward Citations)
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