US4393050A
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Analogs of extended N-terminal somatostatin
Assignee: Salk Institute for Biological Studies
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Filing: 1981-04-29
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Granted: 1983-07-12
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Expires: 2001-04-29
Abstract
Abstract Somatostatin-28 has the formula: H-Ser-Ala-Asn-Ser-Asn-Pro-Ala-Met-Ala-Pro-Arg-Glu-Arg-Lys- +TR <IMAGE> Analogs have been synthesized that are more potent than somatostatin-28, and these analogs or pharmaceutically acceptable salts thereof, dispersed in a pharmaceutically acceptable liquid or solid carrier, can be administered to mammals in the same manner as somatostatin. In the analogs, Leu may be substituted in the 8-position in combination with D-Trp in the 22-position and/or Tyr in the 25-position. D-Cys may also be substituted in the 28-position, and D-Ser may be substituted in the 27-position. Certain residues may also be deleted. D-Trp22 somatostation-28 has surprisingly been found to be insulin-selective when administered in vivo and is useful for the treatment of insulinoma.
Inventors
- 👤 Wylie W. Vale, Jr.
- 👤 Jean E. F. Rivier
- 👤 Marvin R. Brown
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-01 19:58
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/575; C07K14/655; C07K14/6555; A; A61; A61P; A61P5/00; A61P5/02; A61K; A61K38/00; Y; Y10; Y10S; Y10S930/00; Y10S930/01; Y10S930/16
Claims Analysis
Total Claims: 20
Claim 1
Independent Claim
83 words
A pharmaceutical composition for decreasing gastric acid secretion comprising an effective amount of an analog of SS-28 having the formula: ##STR6## wherein R 18 is Lys or des R 18 , R 19 is Asn or des R 19 , R 25 is Phe or Tyr, R 26 is Thr or des R 26 , R 27 is Ser or D--Ser and R 28 is D--Cys or Cys, or a nontoxic addition salt thereof, and a pharmaceutically acceptable liquid or solid carrier therefor.
Claim 2
Dependent Claim
83 words
A pharmaceutical composition for decreasing gastric acid secretion comprising an effective amount of an analog of SS-28 having the formula: ##STR6## wherein R 18 is Lys or des R 18 , R 19 is Asn or des R 19 , R 25 is Phe or Tyr, R 26 is Thr or des R 26 , R 27 is Ser or D--Ser and R 28 is D--Cys or Cys, or a nontoxic addition salt thereof, and a pharmaceutically acceptable liquid or solid carrier therefor.
Claim 3
Dependent Claim
27 words
The composition of claim 1 wherein R 18 is Lys, R 19 is Asn, R 26 is Thr, R 27 is Ser and R 28 is Cys.
Claim 4
Dependent Claim
10 words
The composition of claim 2 wherein R 25 is Phe.
Claim 5
Dependent Claim
10 words
The composition of claim 2 wherein R 25 is Tyr.
Claim 6
Independent Claim
110 words
A method of inhibiting the release of growth hormone, insulin, adrenal epenephrine and or glucagon in a mammal or modifying the temperature regulation or the gastrointestinal function of a mammal, which method comprises administering to said mammal an effective amount of a material selected from the class consisting of analogs of SS-28 having the formula: ##STR7## wherein R 18 is Lys or des R 18 , R 19 is Asn or des R 19 , R 25 is Phe or Tyr, R 26 is Thr or des R 26 , R 27 is Ser or D-Ser and R 28 is D-Cys or Cys and the nontoxic acid addition salts thereof.
Claim 7
Independent Claim
110 words
A method of inhibiting the release of growth hormone, insulin, adrenal epenephrine and or glucagon in a mammal or modifying the temperature regulation or the gastrointestinal function of a mammal, which method comprises administering to said mammal an effective amount of a material selected from the class consisting of analogs of SS-28 having the formula: ##STR7## wherein R 18 is Lys or des R 18 , R 19 is Asn or des R 19 , R 25 is Phe or Tyr, R 26 is Thr or des R 26 , R 27 is Ser or D-Ser and R 28 is D-Cys or Cys and the nontoxic acid addition salts thereof.
Claim 8
Dependent Claim
20 words
A method in accordance with claim 5 wherein said administering is carried out either orally, intravenously, subcutaneously, intranasally or intramuscularly.
Claim 9
Dependent Claim
27 words
The method of claim 5 wherein R 18 is Lys, R 19 is Asn, R 26 is Thr, R 27 is Ser and R 28 is Cys.
Claim 10
Dependent Claim
10 words
The method of claim 5 wherein R 25 is Phe.
Claim 11
Dependent Claim
10 words
The method of claim 5 wherein R 25 is Tyr.
Claim 12
Dependent Claim
61 words
##STR8## wherein R 18 is Lys or des R 18 , R 19 is Asn or des R 19 , R 25 is Phe or Tyr, R 26 is Thr or des R 26 , R 27 is Ser or D-Ser and R 28 is D--Cys or Cys, or the linear version thereof where the disulfide bridge is replaced by hydrogen.
Claim 13
Dependent Claim
61 words
##STR8## wherein R 18 is Lys or des R 18 , R 19 is Asn or des R 19 , R 25 is Phe or Tyr, R 26 is Thr or des R 26 , R 27 is Ser or D-Ser and R 28 is D--Cys or Cys, or the linear version thereof where the disulfide bridge is replaced by hydrogen.
Claim 14
Dependent Claim
27 words
The compound of claim 10 wherein R 18 is Lys, R 19 is Asn, R 26 is Thr, R 27 is Ser and R 28 is Cys.
Claim 15
Dependent Claim
10 words
The compound of claim 11 wherein R 25 is Phe.
Claim 16
Dependent Claim
10 words
The compound of claim 11 wherein R 25 is Tyr.
Claim 17
Dependent Claim
79 words
##STR9## wherein R 8 is Met or Leu, R 18 is Lys or des R 18 , R 19 is Asn or des R 19 , R 25 is Phe or Tyr, R 26 is Thr or des R 26 , R 27 is Ser or D-Ser and R 28 is D-Cys or Cys, provided however that when R 27 is Ser, R 28 is D-Cys, or the linear version thereof where the disulfide bridge is replaced by hydrogen.
Claim 18
Dependent Claim
79 words
##STR9## wherein R 8 is Met or Leu, R 18 is Lys or des R 18 , R 19 is Asn or des R 19 , R 25 is Phe or Tyr, R 26 is Thr or des R 26 , R 27 is Ser or D-Ser and R 28 is D-Cys or Cys, provided however that when R 27 is Ser, R 28 is D-Cys, or the linear version thereof where the disulfide bridge is replaced by hydrogen.
Claim 19
Dependent Claim
27 words
The compound of claim 14 wherein R 8 is Met, R 18 is Lys, R 25 is Phe, R 27 is D-Ser and R 28 is Cys.
Claim 20
Dependent Claim
37 words
The compound of claim 14 wherein R 8 is Met, R 18 is des R 18 , R 26 is des R 26 , R 25 is Phe, R 27 is Ser and R 28 is D-Cys.
References Cited (Backward Citations)
GB1551929A
Cited
US4316891A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1986-07-11 | 1987-01-10 | 1987-07-12 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1990-07-11 | 1991-01-10 | 1991-07-12 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1994-07-11 | 1995-01-10 | 1995-07-12 | $7700.00 | Window Closed / Lapsed |