US4254106A
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Biologically active amides
Assignee: SmithKline Beecham Corp
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Filing: 1979-09-10
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Granted: 1981-03-03
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Expires: 1999-09-10
Abstract
Abstract The present invention provides novel peptides of formula (I): R--(X.sup.1).sub.m --(X.sup.2).sub.n --X.sup.3 --X.sup.4 --X.sup.5 --X 6 --X 7 --(X 8 ) p --(X 9 ) q --R 1 (I) together with their salts, esters, amides, N-alkylamides and N,N-dialkylamides and acid addition salts thereof. These compounds exhibit morphine agonist activity in both in vitro and in vivo tests and may be used in the treatment of mammals in the fields of both human and veterinary medicine in any condition where an agent with a morphine-like effect is indicated.
Inventors
- 👤 Samuel Wilkinson
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 09:20
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/665; C07K14/70; C07K14/702; C07K14/675; C07K14/6755; A; A61; A61K; A61K38/00
Claims Analysis
Total Claims: 31
Claim 1
Independent Claim
51 words
A compound of the formula: H.Tyr.Gly.Gly.Phe.X.sup.7.OR wherein: X 7 is selected from the group consisting of Ile, Nle,Pro, Val, Ala, NVa, D-Leu and D-Met; R is lower alkyl of 1 to 6 carbon atoms; and the stereochemical configuration of the Tyr and Phe residues may independently be D, L or DL.
Claim 2
Dependent Claim
51 words
A compound of the formula: H.Tyr.Gly.Gly.Phe.X.sup.7.OR wherein: X 7 is selected from the group consisting of Ile, Nle,Pro, Val, Ala, NVa, D-Leu and D-Met; R is lower alkyl of 1 to 6 carbon atoms; and the stereochemical configuration of the Tyr and Phe residues may independently be D, L or DL.
Claim 3
Dependent Claim
22 words
A compound according to claim 1 or a salt, ester, amide, N-alkylamide or N,N-alkylamide or a pharmaceutically acceptable acid addition salt thereof.
Claim 4
Dependent Claim
20 words
A pharmacologically and pharmaceutically acceptable salt or acid addition salt of a compound or derivatives thereof according to claim 1.
Claim 5
Dependent Claim
33 words
A compound according to claim 1 wherein X 7 is D-Leu and R is methyl, or a salt, ester, amide, N-alkylamide or N,N-dialkylamide , thereof, or a pharmaceutically acceptable acid addition salt thereof.
Claim 6
Dependent Claim
32 words
A compound according to claim 1 wherein X 7 is D-Met and R is methyl, or a salt, ester amide, N-alkylamide or N,N-dialkyamide thereof, or a pharmaceutically acceptable acid addition salt thereof.
Claim 7
Dependent Claim
95 words
A pharmaceutical formulation for obtaining a morphine-like effect comprising a pharmaceutically acceptable carrier and an effective morphine-like treatment amount of a compound of the formula: H.Tyr.Gly.Gly.Phe.X.sup.7.OR or a pharmacologically and pharmaceutically acceptable salt, ester, amide, N-alkylamide or N,N-dialkylamide thereof, or a pharmacologically and pharmaceutically acceptable acid addition salt thereof, wherein: X 7 is selected from the groups consisting of Ile, Nle, Pro, Val, Ala, NVa, D-Leu and D-Met; R is lower alkyl of 1 to 6 carbon atoms; and the stereochemical configuration of the Tyr and Phe residues may independently be D, L or DL.
Claim 8
Dependent Claim
95 words
A pharmaceutical formulation for obtaining a morphine-like effect comprising a pharmaceutically acceptable carrier and an effective morphine-like treatment amount of a compound of the formula: H.Tyr.Gly.Gly.Phe.X.sup.7.OR or a pharmacologically and pharmaceutically acceptable salt, ester, amide, N-alkylamide or N,N-dialkylamide thereof, or a pharmacologically and pharmaceutically acceptable acid addition salt thereof, wherein: X 7 is selected from the groups consisting of Ile, Nle, Pro, Val, Ala, NVa, D-Leu and D-Met; R is lower alkyl of 1 to 6 carbon atoms; and the stereochemical configuration of the Tyr and Phe residues may independently be D, L or DL.
Claim 9
Dependent Claim
26 words
The formulation of claim 6 which comprises a pharmacologically and pharmaceutically acceptable ester of said peptide or a pharmacologically and pharmaceutically acceptable acid addition salt thereof.
Claim 10
Dependent Claim
26 words
The formulation of claim 6 which comprises a pharmacologically and pharmaceutically acceptable amide of said peptide or a pharmacologically and pharmaceutically acceptable acid addition salt thereof.
Claim 11
Dependent Claim
28 words
The formulation of claim 6 which comprises a pharmacologically and pharmaceutically acceptable N-alkylamide or N,N-diakylamide of said peptide or a pharmacologically and pharmaceutically acceptable acid addition salt thereof.
Claim 12
Dependent Claim
20 words
The formulation of claim 6, suitable for administration by a route selected from oral, rectal, nasal, buccal, vaginal and parenteral.
Claim 13
Dependent Claim
18 words
The formulation of claim 6, suitable for administration by a route selected from oral, rectal, vaginal and parenteral.
Claim 14
Dependent Claim
23 words
The formulation of claim 6 which comprises the peptide or derivative thereof, or acid addition salt thereof, in solution in an aqueous medium.
Claim 15
Dependent Claim
9 words
The formulation of claim 6 in unit dosage form.
Claim 16
Dependent Claim
37 words
The formulation of claim 13 wherein each unit dosage contains the peptide or derivative thereof, or acid addition salt thereof, in an amount in the range 0.125 μg. to 2g., calculated with reference to the peptide base.
Claim 17
Dependent Claim
15 words
The formulation of claim 6 in the form of a tablet suitable for oral administration.
Claim 18
Dependent Claim
33 words
The formulation of claim 6 wherein said compound is: H.Tyr.Gly.Gly.Phe.D-Leu-OMe or a pharmacologically and pharmaceutically acceptable salt, ester, amide, N-alkylamide or N,N-dialkylamide thereof, or a pharmacologically and pharmaceutically acceptable acid addition salt thereof.
Claim 19
Dependent Claim
33 words
The formulation of claim 6 wherein said compound is: H.Tyr.Gly.Gly.Phe.D-Met.OMe or a pharmacologically and pharmaceutically acceptable salt, ester, amide, N-alkylamide or N,N-dialkylamide thereof, or a pharmacologically and pharmaceutically acceptable acid addition salt thereof.
Claim 20
Independent Claim
109 words
A method for the treatment of a mammal for a condition therein an agent with a morphine-like effect is indicated, comprising the administration to the mammal of an effective morphine-like treatment, non-toxic amount of a peptide of the formula: H-Tyr.Gly.Gly.Phe.X.sup.7.OR or a pharmacologically and pharmaceutically acceptable salt, ester, amide, N-alkylamide or N,N-dialkylamide thereof, or a pharmacologically and pharmaceutically acceptable acid addition salt thereof, wherein X 7 is selected from the group consisting of Ile, Nle, Pro, Val, Ala, NVa, D-Leu and D-Met; R is lower alkyl of 1 to 6 carbon atoms; and the stereochemical configuration of the Tyr and Phe residues may independently be D, L or DL.
Claim 21
Independent Claim
109 words
A method for the treatment of a mammal for a condition therein an agent with a morphine-like effect is indicated, comprising the administration to the mammal of an effective morphine-like treatment, non-toxic amount of a peptide of the formula: H-Tyr.Gly.Gly.Phe.X.sup.7.OR or a pharmacologically and pharmaceutically acceptable salt, ester, amide, N-alkylamide or N,N-dialkylamide thereof, or a pharmacologically and pharmaceutically acceptable acid addition salt thereof, wherein X 7 is selected from the group consisting of Ile, Nle, Pro, Val, Ala, NVa, D-Leu and D-Met; R is lower alkyl of 1 to 6 carbon atoms; and the stereochemical configuration of the Tyr and Phe residues may independently be D, L or DL.
Claim 22
Dependent Claim
28 words
The method of claim 18 which comprises administration of a pharmacologically and pharmaceutically acceptable ester of said peptide or a pharmacologically and pharmaceutically acceptable acid addition salt thereof.
Claim 23
Dependent Claim
28 words
The method of claim 18 which comprises administration of a pharmacologically and pharmaceutically acceptable amide of said peptide or a pharmacologically and pharmaceutically acceptable acid addition salt thereof.
Claim 24
Dependent Claim
30 words
The method of claim 18 which comprises administration of a pharmacologically and pharmaceutically acceptable N-alkylamide or N,N-dialkylamide of said peptide or a pharmacologically and pharmaceutically acceptable acid addition salt thereof.
Claim 25
Dependent Claim
20 words
The method of claim 18 which comprises administration by a route selected from oral, rectal, nasal, buccal, vaginal and parenteral.
Claim 26
Dependent Claim
18 words
The method of claim 18 which comprises administration by a route selected from oral, rectal, vaginal and parenteral.
Claim 27
Dependent Claim
28 words
The method of claim 18 for the relief of pain, for the suppression of cough, for the induction of constipation or for the treatment of diarrhea or dysentery.
Claim 28
Dependent Claim
42 words
The method of claim 18 wherein the peptide or derivative thereof, or acid addition salt thereof, is administered at a dosage in the range 0.0025 μg. to 40 mg per kilogram bodyweight of the mammal, calculated with reference to the peptide base.
Claim 29
Dependent Claim
10 words
The method of claim 18 wherein the mammal is man.
Claim 30
Dependent Claim
33 words
The method of claim 18 wherein said compound is: H.Tyr.Gly.Gly.Phe.D-Leu.OMe or a pharmacologically and pharmaceutically acceptable salt, ester, amide, N-alkylamide or N,N-dialkylamide thereof, or a pharmacologically and pharmaceutically acceptable acid addition salt thereof.
Claim 31
Dependent Claim
33 words
The method of claim 18 wherein said compound is: H.Tyr.Gly.Gly.Phe.D-Met.OMe or a pharmacologically and pharmaceutically acceptable salt, ester, amide, N-alkylamide or N,N-dialkylamide thereof, or a pharmacologically and pharmaceutically acceptable acid addition salt thereof.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1984-03-02 | 1984-09-01 | 1985-03-03 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1988-03-02 | 1988-09-01 | 1989-03-03 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1992-03-02 | 1992-09-01 | 1993-03-03 | $7700.00 | Window Closed / Lapsed |