Cell growth inhibitory macrocyclic lactones denominated Combretastatin D-1 and Combretastatin D-2

• US 4,940,726 A
• Filed: 04/26/1989
• Issued: 07/10/1990
• Est. Priority Date: 04/26/1989
• Status: Expired due to Term

• Current Assignee: Arizona Board of Regents (University of Arizona)
• Original Assignee: Arizona Board of Regents (University of Arizona)
• Inventors: Pettit, George R., Singh, Sheo B.
• Primary Examiner(s): Bond, Robert T.
• Assistant Examiner(s): RUSSELL, MARK
• Application Number:
  US07/344,005
• Time in Patent Office: 440 Days
• Field of Search: 514/450, 514/908, 514/475, 549/266, 549/267, 549/270
• US Class Current: 514/450
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 321/00 Heterocyclic compounds containing rings having two oxygen atoms as the only ring hetero atoms, not provided for by groups C07D317/00 - C07D319/00
• CPC Class Codes: C07D 493/08 Bridged systems

Abstract

The isolation and elucidation of novel caffrane macrocyclic lactones denominated "Combretastatin D-1" and "Combretastatin D-2", each of which was found to possess unexpected cell growth inhibitory properties. The lactones have the structural formula: ##STR1## wherein: ##STR2##

Claims

1. A cell growth inhibitory macrocyclic lactone having the structural formula:

##STR5## wherein;

##STR6##

2. A macrocyclic lactone according to claim 1 denominated combretastatin D-1 and having the structural formula:

##STR7##

3. A macrocyclic lactone according to claim 1 denominated combretastatin D-2 and having the structural formula:

##STR8##

4. The method of treating a host afflicted with a neoplastic disease characterized by uncontrolled cell growth comprising administering to said host a pharmaceutical preparation containing a pharmacologically acceptable carrier and, as its essential active cell growth inhibitory substance a therapeutically active amount of a macrocyclic lactone having the structural formula:

##STR9## wherein;

##STR10##

5. The method of claim 4 in which said macrocyclic lactone is denominated combretastatin D-1 and X,X is ##STR11##

6. The method of claim 4 in which said macrocyclic lactone is denominated combretastatin D-2 and X, X is CH=CH.

7. A pharmaceutical preparation comprising a pharmacologically acceptable carrier and a pharmaceutically effective amount of a cell growth inhibitory macrocyclic lactone having the structural formula:

##STR12## wherein;

##STR13##

8. A pharmaceutical preparation according to claim 7 in which said macrocyclic lactone is combretastatin D-1 and X,X is ##STR14##

9. A pharmaceutical preparation according to claim 7 in which said macrocyclic lactone is combretastain D-2 and X,X is CH═

CH.