Novel derivatives of arginine vasopressin antagonists

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United States Patent and Trademark Office

Abstract

Description

Compounds acting as antagonists of the antidiuretic/and or vasopressor activity of arginine vasopressin are those of the formula ##STR1## wherein n is 4 or 5; X is (D- or L-)Tyr(R), D-Phe, D-Val, D-Leu, D-Ile, D-Nva, D-Nle, D-Cha, D-Abu, D-Thr, D-Asn, D-Met or D-Gln; Y is Val, Ile, Thr, Ala, Lys, Cha, Nva, Met, Nle, Orn, Ser, Asn, Gln, Phe, Tyr, Gly, Abu or Leu; Z is (D- or L-) Arg, Orn or Lys; Q is Arg(NH2), Ser(NH2), (D- or L-)Ala(NH2), Gly, OH or NH2 and R is methyl, ethyl, propyl or butyl; provided that, when Y is Gln or Val, R may also be H. Further compounds are those wherein Q is NH(CH2)3-6 NH2, NH(CH2)2-6 OH, NHalk or NHbzl, provided that when Y is Val, Q is other than NHalk or NHbzl. Other compounds are those wherein Q is M-P, wherein M is Gly, (D- or L-)beta-Ala, (D- or L-)Ala, Sar, Orn, Val, Phe, Ile, Thr, Pro, Tyr, Arg or Ser and P is NHalk, NHbzl, NH(CH2)2-6 OH, NH(CH2)2-6 NH2 or OH, provided that when M is Gly, P is other than OH, and that when M is (D-or L-)beta-Ala, P is also NH2. Further compounds include decapeptides wherein Q is M-A-P', wherein M and A are selected independently from Gly, (D- or L-)beta-Ala, (D-or L-)Ala, Sar, Orn, Val, Phe, Ile, Thr, Pro, Tyr, Arg or Ser and P' is OH, NH2, NHalk, NH(CH2)2-6 NH2, NHbzl or NH(CH2)2-6 OH. Additional compounds include those wherein X is D-Tyr.

Keywords

514/10.9, 514/15.4, 514/21.1, 514/807, 530/315, 930/20, 930/21, 930/150, 930/DIG.565, 930/DIG.566, 930/DIG.567

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