Cyclic adhesion inhibitors

US6001961A · kind A · utility

Assignee

• Merck Patent GmbH · DE

Inventors

• Alfred Jonczyk · Darmstadt, DE
• Simon Goodman
• Beate Diefenbach · Darmstadt, DE
• Arne Sutter · Darmstadt, DE
• Gunter Holzemann · Seeheim-Jugenheim, DE
• Horst Kessler · Schwalbach, DE
• Michael Dechantsreiter · Cambridge, US

Key dates

• Filing date: Sep 16, 1996
• Grant date: Dec 14, 1999
• Expiry date: Sep 16, 2016

Classification

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

Abstract

The invention relates to novel cyclopeptides of the formula I EQU cyclo-(nArg-nGly-nAsp-nD-nE) I, in which PA1 D and E in each case independently of one another are Gly, Ala, .beta.-Ala, Asn, Asp, Asp(OR), Arg, Cha, Cys, Gln, Glu, His, Ile, Leu, Lys, Lys(Ac), Lys(AcNH.sub.2), Lys(AcSH), Met, Nal, Nle, Orn, Phe, 4-Hal-Phe, homo-Phe, Phg, Pro, Pya, Ser, Thr, Tia, Tic, Trp, Tyr or Val, which amino acid residues can also be derivatized, PA1 R is alkyl having 1-18 carbon atoms, PA1 Hal is F, Cl, Br, I, PA1 Ac is alkanoyl having 1-10 carbon atoms, aroyl having 7-11 carbon atoms or aralkanoyl having 8-12 carbon atoms, PA1 n denotes no substituent or an alkyl radical R, benzyl or an aralkyl radical having 7-18 carbon atoms on the alpha-amino function of the relevant amino acid residue, with the proviso that at least one amino acid residue has a substituent n and that, where residues of optically active amino acids and amino acid derivatives are involved, both the D and the L forms are included, and also their physiologically acceptable salts. These compounds act as integrin inhibitors and can be used in particular for the prophylaxis and treatment of disorders of the circulation, angiogeni…