US4178371A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Tetrapeptide derivatives
Assignee: COLMAN PRODUCTS Ltd
•
Filing: 1978-11-27
•
Granted: 1979-12-11
•
Expires: 1998-11-27
Abstract
Abstract Tetrapeptide amides of the formula ##STR1## wherein R 1 , R 8 , R x , B and D represent certain specified substituent groups. The compounds exhibit pharmacological activity when tested in vitro in the transmurally stimulated guinea pig ileum preparation indicating their affinity for opiate receptor sites, and also in vivo tests, with intravenous administration, indicating their analgesic effects, and hence their utility as analgesic agents.
Inventors
- 👤 Barry A. Morgan
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-02 16:11
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/665; C07K14/70; C07K14/702; A; A61; A61P; A61P1/00; A61P1/12; A61P25/00; A61P25/04; A61P25/30; C07C; C07C275/00; C07C275/04; C07C275/06; C07C275/14; C07K5/00; C07K5/04; C07K5/10; C07K5/1002; C07K5/1016
Claims Analysis
Total Claims: 16
Claim 1
Independent Claim
268 words
A compound of the formula: ##STR28## wherein R 1 is hydrogen, methyl, allyl, dimethylallyl, propargyl, cycloproplmethyl, cyclobutylmethyl or phenethyl; B is the group --NH--CR.sup.3 H--CO-- in which R 3 is alkyl C 1-6 or C q H 2q YC r H 2r+1 (where q is 1-2, r is 0-1 and Y is O, S, SO or SO 2 ); the group having the D-configuration; D is the group --NR.sup.5 --CR.sup.6 H--CO-- in which R 5 is hydrogen or methyl; R 6 Ar-alkyl C 1-3 ; the group having the L-configuration; R 8 is hydrogen, alkyl C 1-5 , Ar or Ar-alkyl C 1-2 ; R x is a group (CH 2 ) s --X where s is 2-4 and X is NHR 9 , N⊕R 11 R 12 R 13 , NR 9 COR 11 , NR 9 COOR 11 , NR 9 CONH 2 , NR 9 CONR 10 R 11 , N(O) n R 11 R 12 , COOR 9 , CONR 9 R 10 , or OCONR 9 R 10 (where R 9 is hydrogen, alkyl C 1-3 , Ar or ArCH 2 ; R 10 is hydrogen or alkyl C 1-3 ; R 11 is alkyl C 1-3 , Ar or ArCH 2 ; R 12 is alkyl C 1-3 ; R 13 is alkyl C 1-3 ; and n is 0 or 1); or the group ##STR29## where m is 1-3 and Q is SO, SO 2 , CO CHOH, N⊕MeR 11 or N(O)R 11 ; Ar is phenyl or phenyl substituted by chlorine, methyl, hydroxy or methoxy; and their acid addition salts.
Claim 2
Dependent Claim
268 words
A compound of the formula: ##STR28## wherein R 1 is hydrogen, methyl, allyl, dimethylallyl, propargyl, cycloproplmethyl, cyclobutylmethyl or phenethyl; B is the group --NH--CR.sup.3 H--CO-- in which R 3 is alkyl C 1-6 or C q H 2q YC r H 2r+1 (where q is 1-2, r is 0-1 and Y is O, S, SO or SO 2 ); the group having the D-configuration; D is the group --NR.sup.5 --CR.sup.6 H--CO-- in which R 5 is hydrogen or methyl; R 6 Ar-alkyl C 1-3 ; the group having the L-configuration; R 8 is hydrogen, alkyl C 1-5 , Ar or Ar-alkyl C 1-2 ; R x is a group (CH 2 ) s --X where s is 2-4 and X is NHR 9 , N⊕R 11 R 12 R 13 , NR 9 COR 11 , NR 9 COOR 11 , NR 9 CONH 2 , NR 9 CONR 10 R 11 , N(O) n R 11 R 12 , COOR 9 , CONR 9 R 10 , or OCONR 9 R 10 (where R 9 is hydrogen, alkyl C 1-3 , Ar or ArCH 2 ; R 10 is hydrogen or alkyl C 1-3 ; R 11 is alkyl C 1-3 , Ar or ArCH 2 ; R 12 is alkyl C 1-3 ; R 13 is alkyl C 1-3 ; and n is 0 or 1); or the group ##STR29## where m is 1-3 and Q is SO, SO 2 , CO CHOH, N⊕MeR 11 or N(O)R 11 ; Ar is phenyl or phenyl substituted by chlorine, methyl, hydroxy or methoxy; and their acid addition salts.
Claim 3
Dependent Claim
216 words
A compound of the formula ##STR30## wherein R 1 is hydrogen, methyl, allyl, dimethylallyl, propargyl, cyclopropylmethyl, cyclobutylmethyl or phenethyl; B is the group --NH--CR.sup.3 H--CO-- in which R 3 is alkyl C 1-6 or C q H 2q YC r H 2r+1 (where q is 1-2, r is 0-1 and Y is O, S, SO or SO 2 ), the group having the D-configuration; D is the group --NR.sup.5 --CR.sup.6 H--CO-- in which R 5 is hydrogen or methyl; R 6 is Ar-alkyl C 1-3 , the group having the L-configuration; R 8 is hydrogen or alkyl C 1-5 ; R x is a group (CH 2 ) s --X where s is 2-4 and X is NHR 9 , NR 9 COR 11 , NR 9 CONH 2 , NR 9 CONR 10 R 11 , N(O) n R 11 R 12 , COOR 9 , CONR 9 R 10 , NR 9 COOR 11 or OCONR 9 R 10 (where R 9 is hydrogen or alkyl C 1-3 ; R 10 is hydrogen or alkyl C 1-3 ; R 11 is alkyl C 1-3 ; R 12 is alkyl C 1-3 and n is 0 or 1); Ar is phenyl or phenyl substituted by chlorine, methyl, hydroxy or methoxy; and their acid addition salts.
Claim 4
Dependent Claim
216 words
A compound of the formula ##STR30## wherein R 1 is hydrogen, methyl, allyl, dimethylallyl, propargyl, cyclopropylmethyl, cyclobutylmethyl or phenethyl; B is the group --NH--CR.sup.3 H--CO-- in which R 3 is alkyl C 1-6 or C q H 2q YC r H 2r+1 (where q is 1-2, r is 0-1 and Y is O, S, SO or SO 2 ), the group having the D-configuration; D is the group --NR.sup.5 --CR.sup.6 H--CO-- in which R 5 is hydrogen or methyl; R 6 is Ar-alkyl C 1-3 , the group having the L-configuration; R 8 is hydrogen or alkyl C 1-5 ; R x is a group (CH 2 ) s --X where s is 2-4 and X is NHR 9 , NR 9 COR 11 , NR 9 CONH 2 , NR 9 CONR 10 R 11 , N(O) n R 11 R 12 , COOR 9 , CONR 9 R 10 , NR 9 COOR 11 or OCONR 9 R 10 (where R 9 is hydrogen or alkyl C 1-3 ; R 10 is hydrogen or alkyl C 1-3 ; R 11 is alkyl C 1-3 ; R 12 is alkyl C 1-3 and n is 0 or 1); Ar is phenyl or phenyl substituted by chlorine, methyl, hydroxy or methoxy; and their acid addition salts.
Claim 5
Dependent Claim
26 words
A compound as claimed in claim 1 or claim 2 wherein B is D-alanine, D-α-aminobutyric acid, D-valine, D-norvaline, D-leucine, D-norleucine, D-serine, D-threonine, D-methionine or D-methionine sulphoxide.
Claim 6
Dependent Claim
16 words
A compound as claimed in claim 1 or claim 2 wherein D is L-phenylalanine or N-methyl-L-phenylalanine.
Claim 7
Dependent Claim
8 words
A compound of claim 1 which is L-tyrosyl-D-alanylglycyl-L-phenylalanine-2-acetamidoethylamide.
Claim 8
Dependent Claim
8 words
A compound of claim 1 which is L-tyrosyl-D-alanylglycyl-N-methyl-L-phenylalanine-3-dimethylaminopropylamide.
Claim 9
Dependent Claim
8 words
A compound of claim 1 which is L-tyrosyl-D-alanylglycyl-N-methyl-L-phenylalanine-3-dimethylaminopropylamide-N-oxide.
Claim 10
Dependent Claim
8 words
A compound of claim 1 which is L-tyrosyl-D-alanylglycyl-N-methyl-L-phenylalanine-2-dimethylaminoethylamide.
Claim 11
Dependent Claim
8 words
A compound of claim 1 which is L-tyrosyl-D-alanyglycyl-N-methyl-L-phenylalanine-2-dimethylaminoethylamide-N-oxide.
Claim 12
Dependent Claim
8 words
A compound of claim 1 which is L-tyrosyl-D-alanylglycyl-N-methyl-L-phenylalanine-2-aminoethylamide.
Claim 13
Dependent Claim
8 words
A compound of claim 1 which is L-tyrosyl-D-alanylglycyl-N-methyl-L-phenylalanine-γ-aminobutyric-N-methyl-N-phenylamide.
Claim 14
Dependent Claim
14 words
A compound of claim 1 which is selected from the group consisting of ##STR31##
Claim 15
Dependent Claim
32 words
A pharmaceutical composition which comprises an effective amount of at least one compound as claimed in claim 1 or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable diluent or carrier.
Claim 16
Dependent Claim
32 words
A compound as claimed in claim 1 or claim 2 where B is D-alanine, D-α-aminobutyric acid, D-valine, D-norvaline, D-leucine, D-norleucine, D-serine, D-threonine, D-methionine or D-methionine sulphoxide and D is L-phenylalanine or N-methyl-L-phenylalanine.
References Cited (Backward Citations)
No citation records indexed.
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1982-12-10 | 1983-06-11 | 1983-12-11 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1986-12-10 | 1987-06-11 | 1987-12-11 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1990-12-10 | 1991-06-11 | 1991-12-11 | $7700.00 | Window Closed / Lapsed |