US4490364A
Expired / Lapsed
US
⏱️ 0.0 years remaining
CCK Agonists II
Assignee: Salk Institute for Biological Studies
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Filing: 1983-08-12
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Granted: 1984-12-25
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Expires: 2003-08-12
Abstract
Abstract Analogs of CCK(1-8) having dissociated activity with respect to stimulating the contraction of the gall bladder and arresting the secretion of gastric acid. Various analogs also exhibit improved anticonvulsive potency. The peptides are characterized by the following formula: X--R.sub.0 --R.sub.1 --Tyr(Y)--R.sub.3 --R.sub.4 --Trp--R.sub.6 --R.sub.7 --R 8 --NHQ wherein X is H, Suc, Ac, Oxa, Mal, Glt, Prp, Prl or Acr; R 0 is Gln, pGlu, Cys, Tyr, Tyr(OCH 3 ), des--NH 2 --Tyr or desR 0 ; R 1 is Asp, Tyr(OH or SE), Ser(OH or SE), Hyp(OH or SE), Thr(OH or SE), Cys, Tyr(OCH 3 ) or desR 1 ; Y is OH or SE; R 3 is Met, Nva or Nle; R 4 is Gly, D--Cys or D--Ala; R 6 is Met, Nva or Nle; R 7 is Asp, Ser(SE), Thr(SE) or Hyp(SE); R 8 is Phe or Tyr(OCH 3 ); and Q is lower alkyl, fluoro lower alkyl or hydrogen; provided that when R 3 and R 6 are Met and R 7 is Asp then R 4 is D--Ala. A pharmaceutically acceptable salt thereof may also be employed.
Inventors
- 👤 Jean E. F. Rivier
- 👤 Botond Penke
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-26 20:13
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/575; C07K14/595; C07K14/5955; A; A61; A61K; A61K38/00
Claims Analysis
Total Claims: 34
Claim 1
Independent Claim
132 words
A synthetic peptide having the formula: X--R 0 --R 1 --Tyr(Y)--R 3 --R 4 --Trp--R 6 --R 7 --R 8 --NHQ wherein X is H, Suc, Ac, Oxa, Mal, Glt, Prp, Prl or Acr; R 0 is Gln, pGlu, Cys, Tyr, Tyr(OCH 3 ), des--NH 2 --Tyr or desR 0 ; R 1 is Asp, Tyr(OH or SE), Ser(OH or SE), Hyp(OH or Se), Thr(OH or SE), Cys, Tyr(OCH 3 ) or desR 1 ; Y is OH or SE; R 3 is Met, Nva or Nle; R 4 is Gly, D--Cys or D--Ala; R 6 is Met, Nva or Nle; R 7 is Ser(SE), Thr(SE) or Hyp(SE); R 8 is Phe or Tyr(OCH 3 ); and Q is lower alkyl, fluoro lower alkyl or hydrogen; or a pharmaceutically acceptable salt thereof.
Claim 2
Dependent Claim
132 words
A synthetic peptide having the formula: X--R 0 --R 1 --Tyr(Y)--R 3 --R 4 --Trp--R 6 --R 7 --R 8 --NHQ wherein X is H, Suc, Ac, Oxa, Mal, Glt, Prp, Prl or Acr; R 0 is Gln, pGlu, Cys, Tyr, Tyr(OCH 3 ), des--NH 2 --Tyr or desR 0 ; R 1 is Asp, Tyr(OH or SE), Ser(OH or SE), Hyp(OH or Se), Thr(OH or SE), Cys, Tyr(OCH 3 ) or desR 1 ; Y is OH or SE; R 3 is Met, Nva or Nle; R 4 is Gly, D--Cys or D--Ala; R 6 is Met, Nva or Nle; R 7 is Ser(SE), Thr(SE) or Hyp(SE); R 8 is Phe or Tyr(OCH 3 ); and Q is lower alkyl, fluoro lower alkyl or hydrogen; or a pharmaceutically acceptable salt thereof.
Claim 3
Dependent Claim
13 words
A synthetic peptide having the formula of claim 1 wherein X is Ac.
Claim 4
Dependent Claim
13 words
A synthetic peptide having the formula of claim 2 wherein Y is SE.
Claim 5
Dependent Claim
13 words
A synthetic peptide in accordance with claim 3 wherein R 4 is D--Ala.
Claim 6
Dependent Claim
31 words
A synthetic peptide having the formula of claim 4 wherein R 0 is desR 0 , R 1 is desR 1 , R 7 is Hyp(SE) and R 8 is Phe.
Claim 7
Dependent Claim
31 words
A synthetic peptide having the formula of claim 1 wherein R 0 is desR 0 , R 1 is desR 1 , R 4 is Gly and R 8 is Phe.
Claim 8
Dependent Claim
14 words
A synthetic peptide having the formula of claim 6 wherein R 7 is Ser(SE).
Claim 9
Dependent Claim
14 words
A synthetic peptide having the formula of claim 6 wherein R 7 is Thr(SE).
Claim 10
Dependent Claim
14 words
A synthetic peptide having the formula of claim 6 wherein R 7 is Hyp(SE).
Claim 11
Dependent Claim
23 words
A synthetic peptide in accordance with claim 8 wherein X is AC, R 3 and R 6 are Met and Y is OH.
Claim 12
Dependent Claim
23 words
A synthetic peptide in accordance with claim 9 wherein X is Ac, R 3 and R 6 are Met and Y is SE.
Claim 13
Dependent Claim
24 words
A synthetic peptide having the formula of claim 7 wherein X is Ac, R 3 and R 6 are Met and Y is SE.
Claim 14
Dependent Claim
24 words
A synthetic peptide having the formula of claim 8 wherein X is Ac, R 3 and R 6 are Met and Y is SE.
Claim 15
Dependent Claim
16 words
A synthetic peptide in accordance with claim 5 wherein R 3 and R 6 are Met.
Claim 16
Dependent Claim
15 words
A synthetic peptide in accordance with claim 1 wherein R 8 is Tyr(OCH 3 ).
Claim 17
Dependent Claim
16 words
A synthetic peptide in accordance with claim 15 wherein R 3 and R 6 are Nle.
Claim 18
Dependent Claim
35 words
A synthetic peptide having the formula of claim 16 wherein R 0 is desR 0 , R 1 is desR 1 , R 4 is Gly and R 7 is Tyr(SE), Ser(SE), Hyp(SE) or Thr(SE).
Claim 19
Dependent Claim
34 words
A synthetic peptide having the formula of claim 16 wherein R 0 is desR 0 , R 1 is Asp, R 4 is Gly, R 7 is Hyp(OSO 3 Na) and Y is SE.
Claim 20
Dependent Claim
37 words
A pharmaceutical composition for stimulating the contraction of the gall bladder containing an effective amount of the synthetic peptide of claim 13 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable liquid or solid carrier therefor.
Claim 21
Dependent Claim
37 words
A pharmaceutical composition for stimulating the contraction of the gall bladder containing an effective amount of the synthetic peptide of claim 12 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable liquid or solid carrier therefor.
Claim 22
Dependent Claim
37 words
A pharmaceutical composition for stimulating the contraction of the gall bladder containing an effective amount of the synthetic peptide of claim 11 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable liquid or solid carrier therefor.
Claim 23
Dependent Claim
32 words
A pharmaceutical composition for counteracting convulsions in a mammal containing an effective amount of the synthetic peptide of claim 13 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier therefor.
Claim 24
Dependent Claim
32 words
A pharmaceutical composition for counteracting convulsions in a mammal containing an effective amount of the synthetic peptide of claim 14 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier therefor.
Claim 25
Dependent Claim
32 words
A pharmaceutical composition for lowering the secretion of gastric acid comprising an effective amount of the peptide of claim 11 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier therefor.
Claim 26
Dependent Claim
32 words
A pharmaceutical composition for lowering the secretion of gastric acid comprising an effective amount of the peptide of claim 12 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier therefor.
Claim 27
Dependent Claim
32 words
A pharmaceutical composition for lowering the secretion of gastric acid comprising an effective amount of the peptide of claim 13 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier therefor.
Claim 28
Dependent Claim
32 words
A pharmaceutical composition for lowering the secretion of gastric acid comprising an effective amount of the peptide of claim 14 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier therefor.
Claim 29
Independent Claim
160 words
A method for stimulating contraction of the gall bladder comprising administering an effective amount of the synthetic peptide having the formula: X--R 0 --R 1 --Tyr(Y)--R 3 --R 4 --Trp--R 6 --R 7 --R 8 --NHQ wherein X is H, Suc, Ac, Oxa, Mal, Glt, Prp, Prl or Acr; R 0 is Gln, pGlu, Cys, Tyr, Tyr(OCH 3 ), des--NH 2 --Tyr or desR 0 ; R 1 is Asp, Tyr(OH or SE), Ser(OH or SE), Hyp(OH or SE), Thr(OH or SE), Cys, Tyr(OCH 3 ) or desR 1 ; Y is OH or SE; R 3 is Met, Nva or Nle; R 4 is D--Cys or D--Ala; R 6 is Met, Nva or Nle; R 7 is Asp, Ser(SE), Thr(SE) or Hyp(SE); R 8 is Phe or Tyr(OCH 3 ); and Q is lower alkyl, fluoro lower alkyl or hydrogen; provided that either Y is SE or R 7 is other than Asp; or a pharmaceutically acceptable salt thereof.
Claim 30
Independent Claim
160 words
A method for stimulating contraction of the gall bladder comprising administering an effective amount of the synthetic peptide having the formula: X--R 0 --R 1 --Tyr(Y)--R 3 --R 4 --Trp--R 6 --R 7 --R 8 --NHQ wherein X is H, Suc, Ac, Oxa, Mal, Glt, Prp, Prl or Acr; R 0 is Gln, pGlu, Cys, Tyr, Tyr(OCH 3 ), des--NH 2 --Tyr or desR 0 ; R 1 is Asp, Tyr(OH or SE), Ser(OH or SE), Hyp(OH or SE), Thr(OH or SE), Cys, Tyr(OCH 3 ) or desR 1 ; Y is OH or SE; R 3 is Met, Nva or Nle; R 4 is D--Cys or D--Ala; R 6 is Met, Nva or Nle; R 7 is Asp, Ser(SE), Thr(SE) or Hyp(SE); R 8 is Phe or Tyr(OCH 3 ); and Q is lower alkyl, fluoro lower alkyl or hydrogen; provided that either Y is SE or R 7 is other than Asp; or a pharmaceutically acceptable salt thereof.
Claim 31
Dependent Claim
11 words
A method according to claim 28 wherein R 4 is D--Ala.
Claim 32
Independent Claim
159 words
A method of counteracting convulsions in an animal comprising administering an effective amount of a synthetic peptide having the formula: X--R 0 --R 1 --Tyr(Y)--R 3 --R 4 --Trp--R 6 --R 7 --R 8 --NHQ wherein X is H, Suc, Ac, Oxa, Mal, Glt, Prp, Prl or Acr; R 0 is Gln, pGlu, Cys, Tyr, Tyr(OCH 3 ), des--NH 2 --Tyr or desR 0 ; R 1 is Asp, Tyr(OH or SE), Ser(OH or SE), Hyp(OH or SE), Thr(OH or SE), Cys, Tyr(OCH 3 ) or desR 1 ; Y is OH or SE; R 3 is Met, Nva or Nle; R 4 is D--cys or D--Ala; R 6 is Met, Nva or Nle; R 7 is Asp, Ser(SE), Thr(SE) or Hyp(SE); R 8 is Phe or Tyr(OCH 3 ); and Q is lower alkyl, fluoro lower alkyl or hydrogen; provided that either Y is SE or R 7 is other than Asp; or a pharmaceutically acceptable salt thereof.
Claim 33
Independent Claim
159 words
A method of counteracting convulsions in an animal comprising administering an effective amount of a synthetic peptide having the formula: X--R 0 --R 1 --Tyr(Y)--R 3 --R 4 --Trp--R 6 --R 7 --R 8 --NHQ wherein X is H, Suc, Ac, Oxa, Mal, Glt, Prp, Prl or Acr; R 0 is Gln, pGlu, Cys, Tyr, Tyr(OCH 3 ), des--NH 2 --Tyr or desR 0 ; R 1 is Asp, Tyr(OH or SE), Ser(OH or SE), Hyp(OH or SE), Thr(OH or SE), Cys, Tyr(OCH 3 ) or desR 1 ; Y is OH or SE; R 3 is Met, Nva or Nle; R 4 is D--cys or D--Ala; R 6 is Met, Nva or Nle; R 7 is Asp, Ser(SE), Thr(SE) or Hyp(SE); R 8 is Phe or Tyr(OCH 3 ); and Q is lower alkyl, fluoro lower alkyl or hydrogen; provided that either Y is SE or R 7 is other than Asp; or a pharmaceutically acceptable salt thereof.
Claim 34
Dependent Claim
11 words
A method according to claim 30 wherein R 4 is D--Ala.
References Cited (Backward Citations)
US4330466A
Cited
US4351829A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1987-12-25 | 1988-06-25 | 1988-12-25 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-12-25 | 1992-06-25 | 1992-12-25 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-12-25 | 1996-06-25 | 1996-12-25 | $7700.00 | Window Closed / Lapsed |