Patent US4448715A successfully refreshed from Google Patents.
US4448715A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Tagged pyroglu-L-Phe-L-Arg derivatives, substrates and assays for kallikrein
Assignee: University of Miami
•
Filing: 1981-11-02
•
Granted: 1984-05-15
•
Expires: 2001-11-02
Abstract
Abstract Novel compositions of matter of the general formula A--L--Phe--L--Arg--Y are described, in which A is lower alkanoyl, pyroglutamyl, substituted with --OH or halogen, and cyclo lower alkanoyls; Y is --OH or a known tag with either radioactive, fluorogenic, chromogenic or chemiluminescent properties. The compounds of the invention are useful as novel substrates for plasma kallikrein. A new method of performing the assay for plasma kallikrein is also described.
Inventors
- 👤 James W. Ryan
- 👤 Alfred Chung
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 03:35
CPC Classifications
C; C12; C12Q; C12Q1/00; C12Q1/34; C12Q1/37; C07; C07K; C07K5/00; C07K5/04; C07K5/06; C07K5/06008; C07K5/06078; C07K5/08; C07K5/0821; C07K5/0825
Claims Analysis
Total Claims: 15
Claim 1
Independent Claim
123 words
Novel compounds of the general formula: A--L--phe--L--arg--Y, or methyl esters thereof or ethyl esters thereof, wherein, group A contains a carbonyl moiety in amide linkage with the α-amino group of L--Phe and is any one of the groups consisting essentially of cyclopropanecarbonyl, cyclobutanecarbonyl, cyclopentanecarbonyl, cyclohexanecarbonyl, pyroglutamyl, 3,4-dehydroprolyl, 4-ketoprolyl, 4-OH-prolyl, 3-OH-prolyl, 3-phenylpropanoyl, thioprolyl, azetidine-2-carbonyl, thiazolidine-4-carbonyl, 5-X-prolyl, 4-X-prolyl, 3-X-prolyl, and 2-X-prolyl wherein X of any of the last four radicals is halo; and group Y is joined to the α-carbonyl of L--Arg to form an ester or amide linkage therewith and is --OH or any known indicator that is radioactively or chemiluminescently tagged or which comprises a chromogen or fluorogen except that when A is pyroglutamyl Y is a radioactively or chemiluminescently tagged benzylamide group.
Claim 2
Dependent Claim
123 words
Novel compounds of the general formula: A--L--phe--L--arg--Y, or methyl esters thereof or ethyl esters thereof, wherein, group A contains a carbonyl moiety in amide linkage with the α-amino group of L--Phe and is any one of the groups consisting essentially of cyclopropanecarbonyl, cyclobutanecarbonyl, cyclopentanecarbonyl, cyclohexanecarbonyl, pyroglutamyl, 3,4-dehydroprolyl, 4-ketoprolyl, 4-OH-prolyl, 3-OH-prolyl, 3-phenylpropanoyl, thioprolyl, azetidine-2-carbonyl, thiazolidine-4-carbonyl, 5-X-prolyl, 4-X-prolyl, 3-X-prolyl, and 2-X-prolyl wherein X of any of the last four radicals is halo; and group Y is joined to the α-carbonyl of L--Arg to form an ester or amide linkage therewith and is --OH or any known indicator that is radioactively or chemiluminescently tagged or which comprises a chromogen or fluorogen except that when A is pyroglutamyl Y is a radioactively or chemiluminescently tagged benzylamide group.
Claim 3
Dependent Claim
64 words
A compound according to claim 1 wherein A is not pyroglutamyl and Y is a radioactively tagged group and is any one of the group consisting essentially of [ 3 H]-anilino, [ 3 H]-benzylamino, [ 14 C]-anilino, [ 14 C]-benzylamino, [ 3 H]-methoxy, [ 3 H]-ethoxy, [ 14 C]-methoxy, [ 14 C]-ethoxy, 4-Z-naphthyl-2-amino, 4-Z-naphthyl-1-amino, Z-hydroxyanilino, Z-hydroxybenzylamino and 5-Z-coumaryl-7-amino, wherein Z is a radioactive halogen.
Claim 4
Dependent Claim
49 words
A compound according to claim 1 wherein A is not pyroglutamyl and Y is a chromogenic tag and is any one of the group consisting essentially of p-NO 2 -anilino, p-NO 2 -phenyloxy, nitrophenylamino, naphthylamino, nitronaphthylamino, methoxynaphthylamino, quinolylamino, nitroquinolylamino, 4-trifluoromethyl coumaryl-7-amino, 4-Z-naphthyl-1-amino and 4-Z-naphthyl-2-amino, wherein Z is radioactive halogen.
Claim 5
Dependent Claim
49 words
A compound according to claim 1 wherein A is not pyroglutamyl and Y is a fluorogenic tag and is any one of the group consisting essentially of 4-methyl coumaryl-7-amino, 4-trifluoromethyl coumaryl-7-amino, naphthylamino, 7-oxy-coumaryl, 5-amino isophthallic acid dimethyl ester, 5-Z coumaryl-7-amino, 4-Z-naphthyl-1-amino and 4-Z-naphthyl-2-amino, wherein Z is a radioactive tag.
Claim 6
Dependent Claim
15 words
A compound according to claim 1 wherein Y is a chemiluminescent tag and is amino-iso-luminol.
Claim 7
Dependent Claim
36 words
A compound according to claim 1 wherein Y is a radioactively tagged group and is any one of the group consisting essentially of [ 3 H]-anilino, [ 3 H]-benzylamino, [ 14 C]-anilino and [ 14 C]-benzylamino.
Claim 8
Dependent Claim
30 words
A compound according to claim 1 wherein A is not pyroglutamyl and Y is a chromogenic tag and is either of the group consisting of p-NO 2 -anilino and 2-naphthylamino.
Claim 9
Dependent Claim
30 words
A compound according to claim 1 wherein A is not pyroglutamyl and Y is a fluorogenic tag and is either of the group consisting of 4-methyl coumaryl-7-amino and 4-trifluoromethyl coumaryl-7-amino.
Claim 10
Dependent Claim
21 words
A compound according to claim 1 wherein A is any of the group consisting essentially of 3-phenyl propanoyl and 4-keto prolyl.
Claim 11
Dependent Claim
83 words
A compound according to claim 1 wherein, group A is 3-phenylpropanoyl or 4-keto prolyl; when group Y is a radioactively tagged group, Y is any one of the group consisting essentially of [ 3 H]-anilino, [ 3 H]-benzylamino, [ 14 C]-anilino, and [ 14 C]-benzylamino; when Y is a chromogenic tag, Y is either of p--NO 2 -anilino and 2-naphthylamino; when Y is a fluorogenic group, Y is either of 4-methyl coumaryl-7-amino and 4-trifluoromethyl coumaryl-7-amino; when Y is chemiluminescent, Y is amino isoluminol.
Claim 12
Dependent Claim
22 words
A compound according to claims 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 wherein Y is [ 3 H]-benzylamino.
Claim 13
Dependent Claim
16 words
A compound according to claim 1 wherein A is pyroglutamyl and Y is [ 3 H]-benzylamino.
Claim 14
Dependent Claim
16 words
A compound according to claim 1 wherein A is phenylpropanoyl and Y is [ 3 H]benzyl.
Claim 15
Dependent Claim
16 words
A compound according to claim 1 wherein A is 4-ketoprolyl and Y is [ 3 H]-benzylamino.
References Cited (Backward Citations)
US3144484A
Cited
US3536588A
Cited
US3591459A
Cited
US3607859A
Cited
US3703441A
Cited
US3773626A
Cited
US3745212A
Cited
US3862011A
Cited
US3884896A
Cited
US3886136A
Cited
US3892631A
Cited
US3769173A
Cited
US4046633A
Cited
US4016042A
Cited
US4028318A
Cited
US4162941A
Cited
US4070245A
Cited
US4214049A
Cited
US4137225A
Cited
US4169015A
Cited
US4061625A
Cited
US4191808A
Cited
US4119620A
Cited
US4138394A
Cited
US4176009A
Cited
US4056519A
Cited
US4116774A
Cited
US4108726A
Cited
US4167449A
Cited
US4207232A
Cited
US4191809A
Cited
US4147692A
Cited
US4115374A
Cited
US4177109A
Cited
US4215047A
Cited
US4188264A
Cited
US4155916A
Cited
US4279810A
Cited
US4234477A
Cited
WO1980000252A1
Cited
US4242329A
Cited
US4216142A
Cited
US4217269A
Cited
US4219497A
Cited
US4327178A
Cited
US4221706A
Cited
US4308202A
Cited
US4244865A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1987-05-15 | 1987-11-14 | 1988-05-15 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-05-15 | 1991-11-14 | 1992-05-15 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-05-15 | 1995-11-14 | 1996-05-15 | $7700.00 | Window Closed / Lapsed |