Pentapeptide compounds and uses related thereto

• US 6,884,869 B2
• Filed: 11/01/2001
• Issued: 04/26/2005
• Est. Priority Date: 04/30/2001
• Status: Expired due to Term

• Current Assignee: Seagen Inc. (Pfizer Inc.)
• Original Assignee: Seattle Genetics Incorporated (Pfizer Inc.)
• Inventors: Doronina, Svetlana, Senter, Peter D., Toki, Brian E.
• Primary Examiner(s): Weber, Jon
• Assistant Examiner(s): Lukton, David
• Application Number:
  US10/001,191
• Publication Number:
  US 20050009751A1
• Time in Patent Office: 1,272 Days
• Field of Search: 530/330, 514/17, 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: A61K 47/6811 the drug being a protein or peptide, e.g. transferrin or bleomycin
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 5/0202 containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
• CPC Class Codes: C07K 5/0205 containing the structure -NH-(X)3-C(=0)-, e.g. statine or derivatives thereof

Abstract

Pentapeptide compounds are disclosed. The compounds have biological activity, e.g., cytotoxicity. Prodrugs having targeting groups and pentapeptide moieities, as well as precursors thereof are also disclosed. For example, precursors having a reactive linker that can serve as a reaction site for joining to a targeting agent, e.g., an antibody, as disclosed.

Claims

1. A compound of the formula

and pharmaceutically acceptable salts and solvates thereof

wherein, independently at each location:

R² is selected from hydrogen and lower alkyl;

R³ is lower alkyl;

R⁴ is selected from lower alkyl, aryl, and —

CH₂—

C_5-7carbocycle when R⁵ is selected from H and methyl, or R⁴ and R⁵ together form a carbocycle of the partial formula —

(CR^aR^b)_n—

wherein R^a and R^b are independently selected from hydrogen and lower alkyl and n is selected from 2, 3, 4, 5 and 6;

R⁶ is selected from hydrogen and lower alkyl;

R⁷ is sec-butyl or iso-butyl;

R⁸ is selected from hydrogen and lower alkyl;

R¹¹ is selected from hydrogen and lower alkyl; and

R¹⁸ is selected from hydrogen, a hydroxyl protecting group, and a direct bond where OR¹⁸ represents ═

O.

2. The compound of claim 1 of the formula

and pharmaceutically acceptable salts and solvates thereof.