Inhibition of phosphatidylinositol 3-kinase with wortmannin and analogs thereof

• US 5,378,725 A
• Filed: 07/19/1993
• Issued: 01/03/1995
• Est. Priority Date: 07/19/1993
• Status: Expired due to Fees

• Current Assignee: Eli Lilly and Company, Arizona Board of Regents (University of Arizona)
• Original Assignee: Eli Lilly and Company, Arizona Board of Regents (University of Arizona)
• Inventors: Bonjouklian, Rosanne, Powis, Garth, Vlahos, Chris J.
• Primary Examiner(s): Henley, III, Raymond J.
• Application Number:
  US08/094,279
• Time in Patent Office: 533 Days
• Field of Search: 514/453, 514/468
• US Class Current: 514/453
• CPC Class Codes: A61K 31/34 having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
• CPC Class Codes: A61K 31/365 Lactones
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Wortmannin and certain of its analogs are inhibitors of phosphatidylinositol 3-kinase. The compounds are particularly useful for inhibiting phosphatidylinositol 3-kinase in mammals and for treating phosphatidylinositol 3-kinase-dependent conditions, especially neoplasms, in mammals.

Claims

1. A method for treating a phosphatidylinositol 3-kinase-dependent neoplasm in a mammal in need of such treatment comprising administering to said mammal a phosphatidylinositol 3-kinase inhibiting amount of a compound selected from the group consisting of ##STR5## wherein R is H or acetoxy;

##STR6## wherein R¹ is H, methyl, or ethyl; and

R² is H or CH₃.

2. The method of claim 1 wherein said mammal is a human.

3. The method of claim 2 wherein said compound is a compound of formula I ##STR7## wherein R is H or acetoxy.

4. The method of claim 3 wherein R is H.

5. The method of claim 3 wherein R is acetoxy.

6. The method of claim 2 wherein said compound is a compound of formula II ##STR8##

7. The method of claim 2 wherein said compound is a compound of formula III ##STR9## wherein R¹ is H, methyl, or ethyl;

and

R² is H or CH₃.

8. The method of claim 7 wherein R¹ is H and R² is H.

9. The method of claim 7 wherein R¹ is methyl and R² is H.