Claims
- 1. A polypeptide compound having the formula: ##STR8## in which:
- A is ##STR9##
- Z is Phe, Phe(4'-Alk) or Tyr(Alk);
- X is D-Phe, D-Phe(4'-Alk), D-Val, D-Nva, D-Leu, D-Ile, D-Pba, D-Nle, D-Cha, D-Abu, D-Met, D-Chg, D-Tyr, L-Tyr, D-Tyr(Alk) or L-Tyr(Alk);
- P is D-Pro, L-Pro, .DELTA..sup.3 -Pro, L-Ala, L-N-MeAla, Gly, Sar or a single bond;
- Y is Val, Ile, Abu, Ala, Chg, Gln, Lys, Cha, Nle, Phe, Leu or Gly;
- R is, in each case, hydrogen or C.sub.1-5 -alkyl;
- n is an integer from 2-8; and
- m is an integer from 0-2; or a pharmaceutically acceptable, acid addition salt thereof.
- 2. The compound of claim 1 in which X is D-Tyr(Et).
- 3. The compound of claim 1 in which X is L-Tyr and Y is Gln.
- 4. The compound of claim 1 in which X is D-Tyr(Et); Z is Phe; Y is Val; P is Pro; m is 0 or 1 and n is 2-6.
- 5. The compound of claim 1 having the formula: ##STR10##
- 6. The compound of claim 1 having the formula: ##STR11##
- 7. The compound of claim 1 having the formula: ##STR12##
- 8. The compound of claim 1 having the formula: ##STR13##
- 9. The compound of claim 1 having the formula: ##STR14##
- 10. A pharmaceutical composition having vasopressin antagonist activity comprising a pharmaceutical carrier and, dispersed therein, an effective therefor but nontoxic quantity of a compound of claim 1.
- 11. The composition of claim 10 in which X is D-Tyr(Et).
- 12. The composition of claim 10 in which the compound has the formula: ##STR15##
- 13. The composition of claim 10 in which the compound has the formula: ##STR16##
- 14. The composition of claim 10 in which the compound has the formula: ##STR17##
- 15. The method of inducing a vasopressin antagonist effect in a patient in need of such an effect comprising administering parenterally or intranasally to said patient a nontoxic, effective quantity therefor of a compound of claim 1.
- 16. The method of claim 15 in which the antagonist effect is manifested by a water diuresis.
- 17. The method of claim 15 in which the compound has the formula: ##STR18##
- 18. The method of claim 15 in which the compound has the formula: ##STR19##
- 19. The method of claim 15 in which the quantity is selected from the range of 0.05-10 mg/kg administered from 1-5 times daily.
- 20. A polypeptide of the formula: ##STR20## in which:
- X is D-Phe, D-Phe(4'-Alk), D-Val, D-Nva, D-Leu, D-Ile, D-Pba, D-Nle, D-Cha, D-Abu, D-Met, D-Chg, D-Tyr, L-Tyr, D-Tyr(Alk) or L-Tyr(Alk);
- Z is Phe, Phe(4'-Alk) or Tyr(Alk);
- Y is Val, Ile, Abu, Ala, Chg, Gln, Lys, Cha, Nle, Phe, Leu or Gly;
- P is D-Pro, L-Pro, .DELTA..sup.3 -Pro, L-Ala, L-N-MeAla, Gly, Sar or a single bond; and
- m is a integer from 0-2; or an acceptable salt or ester thereof.
- 21. The compound of claim 20 being [1-(.beta.-mercapto-.beta.,.beta.-cyclopentamethylenepropionic acid)-2-(O-ethyl-D-tyrosine)-4-valine-8-desarginine-9-desglycinamide]vasopressin.
- 22. The compound of claim 20 being [1-(.beta.-mercapto-.beta.,.beta.-cyclopentamethylenepropionic acid)-2-D-tyrosine-4-valine-8-desarginine-9-desglycinamide]-vasopressin.
- 23. The compound of claim 20 being [1-(.beta.-mercapto-.beta.,.beta.-cyclopentamethylenepropionic acid)-2-(O-ethyl-D-tyrosine)-4-valine-7-desproline-8-desarginine-9-desglycinamide]-vasopressin.
Parent Case Info
This application is a continuation-in-part of Ser. No. 535,000 filed Sept. 22, 1983, now abandoned.
Non-Patent Literature Citations (1)
Entry |
M. Manning, et al., Nature, 308 652 & 653 (1984). |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
535000 |
Sep 1983 |
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