US4427661A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Fluorinated cyclic hexapeptide somatostatin analogs
Assignee: Merck and Co Inc
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Filing: 1982-07-30
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Granted: 1984-01-24
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Expires: 2002-07-30
Abstract
Abstract Fluorinated somatostatin analogs are prepared wherein a cyclic hexapeptide contains a secondary amino acid which replaces seven of the ring amino acids of somatostatin and the Lys side chain is monofluorinated in the gamma or delta positions. The cyclic hexapeptides are easier to synthesize, have a longer duration of activity, and many have a greater level of activity than somatostatin. The compounds have the properties of inhibiting the release of glucagon, growth hormone and insulin. Certain of the compounds also are capable of inhibiting the release of gastric acid secretions. The compounds are particularly useful in the treatment of acromegaly, diabetes, diabetic retinopathy and peptic ulcers. These cyclic hexapeptides are prepared by the solid phase method.
Inventors
- 👤 Paul E. Curley
- 👤 Ralph F. Hirschmann
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 14:54
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/575; C07K14/655; C07K14/6555; A; A61; A61P; A61P5/00; A61K; A61K38/00; Y; Y10; Y10S; Y10S930/00; Y10S930/01; Y10S930/16
Claims Analysis
Total Claims: 10
Claim 1
Independent Claim
141 words
A compound having the formula: ##STR9## wherein Y 1 and Y 2 are hydrogen or fluorine provided Y 1 and Y 2 are not the same; X is (CH 2 ) m wherein m is 0, 1, or 2 or sulfur; R 1 and R 2 are independently lower alkyl, benzyl, substituted benzyl wherein the substituent may be one or two of loweralkyl, halogen, hydroxy, amino, nitro or loweralkoxy; and loweralkyl substituted with a 5 or 6 membered heterocyclic ring; R 3 is 3-indolylmethyl or substituted 3-indolylmethyl wherein the substituent may be loweralkyl, loweralkoxy or halogen; R 4 is loweralkyl, hydroxyloweralkyl, benzyl, carboxyloweralkyl, aminoloweralkyl or substituted hydroxy benzyl wherein the substituent may be loweralkyl, loweralkoxy, hydroxy, halogen, amino or nitro, and R 5 is hydrogen, loweralkyl, benzyl, or substituted benzyl wherein the substituent is loweralkyl, loweralkoxy, hydroxy, halogen, amino or nitro.
Claim 2
Dependent Claim
141 words
A compound having the formula: ##STR9## wherein Y 1 and Y 2 are hydrogen or fluorine provided Y 1 and Y 2 are not the same; X is (CH 2 ) m wherein m is 0, 1, or 2 or sulfur; R 1 and R 2 are independently lower alkyl, benzyl, substituted benzyl wherein the substituent may be one or two of loweralkyl, halogen, hydroxy, amino, nitro or loweralkoxy; and loweralkyl substituted with a 5 or 6 membered heterocyclic ring; R 3 is 3-indolylmethyl or substituted 3-indolylmethyl wherein the substituent may be loweralkyl, loweralkoxy or halogen; R 4 is loweralkyl, hydroxyloweralkyl, benzyl, carboxyloweralkyl, aminoloweralkyl or substituted hydroxy benzyl wherein the substituent may be loweralkyl, loweralkoxy, hydroxy, halogen, amino or nitro, and R 5 is hydrogen, loweralkyl, benzyl, or substituted benzyl wherein the substituent is loweralkyl, loweralkoxy, hydroxy, halogen, amino or nitro.
Claim 3
Dependent Claim
55 words
A compound of claim 1 wherein Y 1 , Y 2 , R 1 and R 2 are as defined in claim 1; R 3 is 3-indolylmethyl or substituted indolylmethyl wherein the substituent is methoxy or fluoro; and R 4 is methyl, ethyl, hydroxymethyl or hydroxyethyl; and R 5 is as defined in claim 1.
Claim 4
Dependent Claim
10 words
A compound of claim 2 wherein R 5 is methyl.
Claim 5
Dependent Claim
33 words
A compound of claim 3 wherein: Y is methylene; R 1 and R 2 are as defined in claim 1; R 3 is 3-indolylmethyl; R 4 is hydroxyethyl; and R 5 is methyl.
Claim 6
Dependent Claim
9 words
The compound of claim 2 which is cyclo (Pro-Phe-D-Trp-γ-F-Lys-Thr-Phe).
Claim 7
Dependent Claim
9 words
The compound of claim 2 which is cyclo (Pro-Phe-D-Trp-δ-F-Lys-Thr-Phe).
Claim 8
Dependent Claim
8 words
The compound of claim 2 which is cyclo(N-Me-Ala-Tyr-D-Trp-γ-F-Lys-Val-Phe).
Claim 9
Dependent Claim
8 words
The compound of claim 2 which is cyclo(N-Me-Ala-Tyr-D-Trp-δ-F-Lys-Val-Phe).
Claim 10
Dependent Claim
40 words
A pharmaceutical composition for inhibiting the release of glucogan, growth hormone and insulin comprising a therapeutically effective amount of the cyclic hexapeptide of claim 1 or the nontoxic acid addition salts thereof in a pharmaceutically acceptable liquid or solid carrier.
References Cited (Backward Citations)
US4235886A
Cited
US4310518A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1987-01-23 | 1987-07-25 | 1988-01-24 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-01-23 | 1991-07-25 | 1992-01-24 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-01-23 | 1995-07-25 | 1996-01-24 | $7700.00 | Window Closed / Lapsed |