Human cancer inhibitory peptide amides

• US 5,530,097 A
• Filed: 08/01/1994
• Issued: 06/25/1996
• Est. Priority Date: 08/01/1994
• Status: Expired due to Term

• Current Assignee: Arizona Board of Regents (University of Arizona)
• Original Assignee: Arizona Board of Regents (University of Arizona)
• Inventors: Williams, Michael D., Pettit, George R., Srirangam, Jayaram K.
• Primary Examiner(s): Nucker, Christine M.
• Assistant Examiner(s): Prickril, Benet
• Application Number:
  US08/283,684
• Time in Patent Office: 694 Days
• Field of Search: 530/321, 530/330, 530/331, 514/18
• 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

Abstract

This application discloses seven newly synthesized pentapeptide amides andour tetrapeptide amides. The synthesis utilized both naturally occurring and modified amino acids; the modified amino acids are constituents of the well known dolastatin 10 and dolastatin 15 which are structurally distinct peptides with excellent antineoplastic activity. These peptides were constructed by introducing a peptide bond between selected amino acids and modified amino acids and coupling the resulting di- and tri-peptides to obtain peptides having a high anticancer activity against a series of human cancer cell lines. ##STR1##

Claims

1. A substantially pure compound having the general structure below:

##STR4## wherein R is selected from the group consisting of;

Met--NH--2ClPh, "8a";

Met --NH--4ClPh, "8b";

Phe--NH--3ClPh, "8c";

Phe--NH--4ClPh, "8d";

Met--NH--BnThz, "8e";

Pro--NH--BnThz, "8f"; and

Met--NH--Q, "8g".

2. A substantially pure compound according to claim 1 wherein R═

Met--NH--2ClPh.

3. A substantially pure compound according to claim 1 wherein R═

Met--NH--4ClPh.

4. A substantially pure compound according to claim 1 wherein R═

Phe--NH--3ClPh.

5. A substantially pure compound according to claim 1 wherein R═

Phe--NH--4ClPh.

6. A substantially pure compound according to claim 1 wherein R═

Met--NH--BnThz.

7. A substantially pure compound according to claim 1 wherein R═

Pro--NH--BnThz.

8. A substantially pure compound according to claim 1 wherein R═

Met--NH--Q.