Cyclic anti-aggregatory peptides

US5643872A · kind A · utility

Assignee

• SmithKline Beecham Limited · US

Inventors

• Fadia E. Ali · Cherry Hill, US
• James Samanen · Phoenixville, US

Key dates

• Filing date: Aug 26, 1994
• Grant date: Jul 1, 1997
• Expiry date: Aug 26, 2014

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K38/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

This invention relates to compounds of the formula: ##STR1## wherein: A' is absent, Asn, Gln, Ala or Abu; PA1 A is absent or a D- or L-amino acid chosen from Arg, HArg, (Me.sub.2)Arg, (Et.sub.2)Arg, Abu, Ala, Gly, His, Lys, or an .alpha.-R' substituted derivative thereof, Dtc, Tpr and Pro; PA1 B is a D- or L-amino acid chosen from Arg, HArg, NArg, (Me.sub.2)Arg, (Et.sub.2)Arg and Lys or an .alpha.-R' substituted derivative thereof; PA1 Q is absent or a D or L amino acid chosen from Tyr, (Alk)Tyr, Phe, (4'W)Phe, HPhe, Phg, Pro, Trp, His, Ser, (Alk)Ser, Thr, (Alk)Thr, (Alk)Cys, (Alk)Pen, Ala, Val, Nva, Met, Leu, Ile, Nle and Nal, or an .alpha.-R' substituted derivative thereof; PA1 M is absent or Gly or a D- or L-amino acid chosen from Glu, Phe, Pro, Lys and Ser or, provided n is 1, B-Gly-Glu-Q; PA1 W is halogen or Alk; PA1 R' is Alk or PhCH.sub.2 ; ##STR2## wherein Z.sub.1 and Z.sub.2 are linked via a covalent bond between L.sup.1 and L.sup.2 ; or Z.sub.1 and Z.sub.2 are, taken together, a covalent bond between the amino terminal residue and the carboxy terminal residue; PA1 L.sup.1 and L.sup.2 are --S-- or --(CH.sub.2).sub.p --; PA1 X is R.sub.4 R.sub.5 N or H; PA1 Y is H, CONR.sub…