Human cancer inhibitory pentapeptide amides

• US 5,410,024 A
• Filed: 01/21/1993
• Issued: 04/25/1995
• Est. Priority Date: 01/21/1993
• Status: Expired due to Term

• Current Assignee: Arizona Board of Regents (University of Arizona)
• Original Assignee: Arizona Board of Regents (University of Arizona)
• Inventors: Kantoci, Darko, Barkoczy, Jozsef, Pettit, George R.
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): MARSHALL, SANDRA GISELE
• Application Number:
  US08/006,465
• Time in Patent Office: 824 Days
• Field of Search: 530/330, 514/17
• US Class Current: 530/330
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 5/0205 containing the structure -NH-(X)3-C(=0)-, e.g. statine or derivatives thereof
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

The synthesis of useful peptides presents a promising approach to new theeutic agents. The Dolastatins, a series of linear and cyclic antineoplastic and/or cytostatic peptides isolated from Indian Ocean sea hare Dolabella auricularia represent excellent leads for synthetic modification.

The extraordinary inhibition of cell growth shown by the pentapeptideamides against six major types of human cancer has been presented. The intermediates of these reaction also show anticancer activity against the murine P388 lymphocytic leukemia cell line.

Claims

1. A compound having the structure:

##STR2## in which R is selected from the group consisting of the substituents designated 9a, 9b, 9c, 9d, 9e, 9g, 9h, 9i, and 9j, as shown below;

##STR3##

2. A compound according to claim 1 wherein ##STR4##

3. A compound according to claim 1 wherein ##STR5##