US4686283A
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Analogs of transforming and epidermal growth factor fragments for therapy and diagnosis
Assignee: Syntex USA LLC
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Filing: 1985-04-16
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Granted: 1987-08-11
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Expires: 2005-04-16
Abstract
Abstract Polypeptides analogs of fragments of TGF alpha and EGF are useful as therapeutic and diagnostic agents.
Inventors
- 👤 John J. Nestor, Jr.
- 👤 Alain B. Schreiber
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 16:29
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/475; C07K14/495; A; A61; A61K; A61K38/00; Y; Y10; Y10S; Y10S930/00; Y10S930/01; Y10S930/12
Claims Analysis
Total Claims: 45
Claim 1
Independent Claim
231 words
A compound represented by the formula ##STR27## the reduced form of said compound or a pharmaceutically acceptable salt of said compound, wherein A is hydrogen, acyl of one to twelve carbon atoms, benzoyl, 3-(4-hydroxyphenyl)propionyl, or 3-(3,5-diiodo-4-hydroxyphenyl)propionyl; B is a bond or a radical of the formula ##STR28## C is (Gly) x or (Ala) x ; D is Val or His; E is Ser, Ile or Val; F is val, Ser or Ile; G is Val, Ala, Asp or Glu; H is (Gly) y or (Ala) y ; I is a bond or a radical represented by formula (II), but independent thereof; and J is OR 7 or NHR 8 , wherein for B, C, H, I and J n is an integer of two to five; each of x and y is independently an integer of zero to five; R 1 is alkyl of one to twelve carbon carbon atoms or --NRR 3 wherein R is hydrogen or lower alkyl and R 3 is hydrogen, alkyl of one to twelve carbon atoms, lower fluoroalkyl, cycloalkyl, phenyl or benzyl; R 2 is hydrogen, alkyl of one to twelve carbon atoms, lower fluoroalkyl, cycloalkyl, phenyl or benzyl R 7 is lower alkyl or hydrogen, provided that R 7 is not hydrogen when A is H, B is a bond and x is 0; and R 8 is hydrogen, lower alkyl or lower fluoroalkyl.
Claim 2
Dependent Claim
231 words
A compound represented by the formula ##STR27## the reduced form of said compound or a pharmaceutically acceptable salt of said compound, wherein A is hydrogen, acyl of one to twelve carbon atoms, benzoyl, 3-(4-hydroxyphenyl)propionyl, or 3-(3,5-diiodo-4-hydroxyphenyl)propionyl; B is a bond or a radical of the formula ##STR28## C is (Gly) x or (Ala) x ; D is Val or His; E is Ser, Ile or Val; F is val, Ser or Ile; G is Val, Ala, Asp or Glu; H is (Gly) y or (Ala) y ; I is a bond or a radical represented by formula (II), but independent thereof; and J is OR 7 or NHR 8 , wherein for B, C, H, I and J n is an integer of two to five; each of x and y is independently an integer of zero to five; R 1 is alkyl of one to twelve carbon carbon atoms or --NRR 3 wherein R is hydrogen or lower alkyl and R 3 is hydrogen, alkyl of one to twelve carbon atoms, lower fluoroalkyl, cycloalkyl, phenyl or benzyl; R 2 is hydrogen, alkyl of one to twelve carbon atoms, lower fluoroalkyl, cycloalkyl, phenyl or benzyl R 7 is lower alkyl or hydrogen, provided that R 7 is not hydrogen when A is H, B is a bond and x is 0; and R 8 is hydrogen, lower alkyl or lower fluoroalkyl.
Claim 3
Dependent Claim
38 words
The compound of claim 1 wherein in formula (I) wherein A is hydrogen, B is a bond, x is an integer of 0 to 2, y is 0, I is a bond and J is NH 2 .
Claim 4
Dependent Claim
27 words
The compound of claim 2 wherein in formula (I) C is Gly, D is His, E is Ser, F is Val, and G is Ala or Val.
Claim 5
Dependent Claim
23 words
The compound of claim 3 wherein in formula (I) G is Val and x is 0, namely ##STR29## or the reduced form thereof.
Claim 6
Dependent Claim
47 words
The compound of claim 1 wherein in formula (I) A is acyl of one to twelve carbon atoms, benzoyl, 3-(4-hydroxyphenyl)propionyl- or 3-(3,5-diiodo-4-hydroxyphenyl)propionyl; B is a bond, x is an integer of zero to 5, y is 0, I is a bond and J is NH 2 .
Claim 7
Dependent Claim
27 words
The compound of claim 5 wherein in formula (1) D is His, E is Ser, F is Val, G is Ala or Val and x is 0.
Claim 8
Dependent Claim
14 words
The compound of claim 6 wherein in formula (I) A is 3-(3,5-diiodo-4-hydroxyphenyl)-propionyl or 3-(4-hydroxyphenyl)-propionyl.
Claim 9
Dependent Claim
46 words
The compound of claim 1 wherein in formula (I) A is hydrogen or acyl of one to twelve carbon atoms, B is the radical of formula (II) wherein R 1 is NRR 3 , C is Gly and x is an integer of one to five.
Claim 10
Dependent Claim
40 words
The compound of claim 8 wherein in formula (II) R is hydrogen, R 2 is alkyl or fluoroalkyl of one to twelve carbon atoms or lower fluoroalkyl and R 3 is hydrogen or alkyl of one to twelve carbon atoms.
Claim 11
Dependent Claim
36 words
The compound o claim 9 wherein in formula (I) y is an integer of two to five, I is a radical of formula (II) wherein R 1 is NRR 3 and J is NHR 8 .
Claim 12
Dependent Claim
20 words
The compound of claim 9 wherein in formula (I) x is 2, y is zero and I is a bond.
Claim 13
Dependent Claim
24 words
The compound of claim 11 wherein in formula (I) D is His, E is Ser, F is Val and G is Val or Ala.
Claim 14
Dependent Claim
12 words
The compound of claim 12 wherein in formula (I) G is Val.
Claim 15
Dependent Claim
38 words
The compound of claim 13 wherein in formula (I) A is acyl of one to twelve carbons, B is L-Deh or D-Deh and J is NHR 8 wherein R 8 is H or CH 2 CH 3 .
Claim 16
Dependent Claim
12 words
The compound of claim 12 wherein in formula (I) G is Ala.
Claim 17
Dependent Claim
33 words
The compound of claim 15 wherein in formula (I) A is acyl of one to twelve carbon atoms, and J is --NHR 8 where R 8 is hydrogen or lower alkyl, namely ##STR30##
Claim 18
Dependent Claim
21 words
The compound of claim 16 wherein in formula (I) R 3 and R 2 are both lower alkyl or lower fluoroalkyl.
Claim 19
Dependent Claim
17 words
The compound of claim 17 wherein in formula (I) R 2 and R 3 are both ethyl.
Claim 20
Dependent Claim
19 words
The compound of claim 12 wherein in formula (I) J is OR 7 and R 7 is lower alkyl.
Claim 21
Dependent Claim
28 words
The compound of claim 11 wherein in formula (I) D is Val, E is Val or Ile, F is Ser or Ile and G if Asp or Glu.
Claim 22
Dependent Claim
17 words
A pharmaceutical composition which comprises a compound of claim 1 in admixture with a pharmaceutically acceptable excipient.
Claim 23
Dependent Claim
10 words
The compound which is: ##STR31## or a reduced form thereof.
Claim 24
Dependent Claim
10 words
The compound which is: ##STR31## or a reduced form thereof.
Claim 25
Dependent Claim
10 words
The compound which is: ##STR32## or a reduced form thereof.
Claim 26
Dependent Claim
10 words
The compound which is: ##STR32## or a reduced form thereof.
Claim 27
Dependent Claim
10 words
The compound which is: ##STR33## or a reduced form thereof.
Claim 28
Dependent Claim
10 words
The compound which is: ##STR33## or a reduced form thereof.
Claim 29
Dependent Claim
10 words
The compound which is: ##STR34## or a reduced form thereof.
Claim 30
Dependent Claim
10 words
The compound which is: ##STR34## or a reduced form thereof.
Claim 31
Dependent Claim
10 words
The compound which is: ##STR35## or a reduced form thereof.
Claim 32
Dependent Claim
10 words
The compound which is: ##STR35## or a reduced form thereof.
Claim 33
Dependent Claim
10 words
The compound which is: ##STR36## or a reduced form thereof.
Claim 34
Dependent Claim
10 words
The compound which is: ##STR36## or a reduced form thereof.
Claim 35
Dependent Claim
10 words
The compound which is: ##STR37## or a reduced form thereof.
Claim 36
Dependent Claim
10 words
The compound which is: ##STR37## or a reduced form thereof.
Claim 37
Dependent Claim
10 words
The compound which is: ##STR38## or a reduced form thereof.
Claim 38
Dependent Claim
10 words
The compound which is: ##STR38## or a reduced form thereof.
Claim 39
Dependent Claim
10 words
The compound which is: ##STR39## or a reduced form thereof.
Claim 40
Dependent Claim
10 words
The compound which is: ##STR39## or a reduced form thereof.
Claim 41
Dependent Claim
18 words
A compound selected from the group consisting of: ##STR40## or a reduced form of any of the above.
Claim 42
Dependent Claim
18 words
A compound selected from the group consisting of: ##STR40## or a reduced form of any of the above.
Claim 43
Dependent Claim
211 words
A compound represented by the formula ##STR41## a reduced form of said compound or a pharmaceutically acceptable salt of said compound, wherein A is hydrogen or acyl of one to twelve carbon atoms; B is a bond or a radical of the formula ##STR42## C is (Gly) x ; D is Val or His; E is Ser, Ile or Val; F is Val, Ser or Ile; G is Val, Ala, Asp or Glu; H is (Gly) y ; I is a bond or a radical represented by formula (II), but independent thereof; and J is OR 7 or NHR 8 ; wherein for B, C, H, I and J n is an integer of two to five; each of x and y is independently an integer of zero to two; R 1 is --NRR 3 wherein R is hydrogen or lower alkyl and R 3 is hydrogen, alkyl of one to twelve carbon atoms, lower fluoroalkyl, or cycloalkyl; R 2 is hydrogen, alkyl of one to twelve carbon atoms, lower fluoroalkyl, cycloalkyl, phenyl or benzyl; R 7 is lower alkyl or hydrogen, provided that R 7 is not hydrogen when A is H, B is a bond and x is 0; and R 8 is hydrogen, lower alkyl or lower fluoroalkyl.
Claim 44
Dependent Claim
211 words
A compound represented by the formula ##STR41## a reduced form of said compound or a pharmaceutically acceptable salt of said compound, wherein A is hydrogen or acyl of one to twelve carbon atoms; B is a bond or a radical of the formula ##STR42## C is (Gly) x ; D is Val or His; E is Ser, Ile or Val; F is Val, Ser or Ile; G is Val, Ala, Asp or Glu; H is (Gly) y ; I is a bond or a radical represented by formula (II), but independent thereof; and J is OR 7 or NHR 8 ; wherein for B, C, H, I and J n is an integer of two to five; each of x and y is independently an integer of zero to two; R 1 is --NRR 3 wherein R is hydrogen or lower alkyl and R 3 is hydrogen, alkyl of one to twelve carbon atoms, lower fluoroalkyl, or cycloalkyl; R 2 is hydrogen, alkyl of one to twelve carbon atoms, lower fluoroalkyl, cycloalkyl, phenyl or benzyl; R 7 is lower alkyl or hydrogen, provided that R 7 is not hydrogen when A is H, B is a bond and x is 0; and R 8 is hydrogen, lower alkyl or lower fluoroalkyl.
Claim 45
Dependent Claim
21 words
The compound of claim 32 wherein A is acyl of one to twelve carbon atoms and R 7 is lower alkyl.
References Cited (Backward Citations)
EP0132021A1
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1990-08-10 | 1991-02-09 | 1991-08-11 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1994-08-10 | 1995-02-09 | 1995-08-11 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1998-08-10 | 1999-02-09 | 1999-08-11 | $7700.00 | Window Closed / Lapsed |