Fatty acid analogues for the treatment of cancer

• US 7,378,443 B2
• Filed: 07/13/2001
• Issued: 05/27/2008
• Est. Priority Date: 07/13/2000
• Status: Expired due to Fees

• Current Assignee: Thia Medica AS (BASF SE)
• Original Assignee: Thia Medica AS (BASF SE)
• Inventors: Berge, Rolf
• Primary Examiner(s): Henley, III; Raymond J.
• Application Number:
  US10/312,901
• Publication Number:
  US 20040024063A1
• Time in Patent Office: 2,510 Days
• Field of Search: 514/549, 514/550, 514/552, 514/558, 514/560
• US Class Current: 514/549
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/20 having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
• CPC Class Codes: A61K 31/22 of acyclic acids, e.g. pravastatin
• CPC Class Codes: A61K 31/23 of acids having a carboxyl group bound to a chain of seven or more carbon atoms
• CPC Class Codes: A61K 31/255 of sulfoxy acids or sulfur analogues thereof
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A fatty acid analogue of the general formula: R₁-[x_i-CH₂]_n—COOR₂, wherein R₁ is: a C₂-C₂₄ alkene with one or more double bonds and/or with one or more triple bonds, and/or a C₂-C₂₄ alkyne, and/or a C₁-C₂₄ alkyl, or a C₁-C₂₄ alkyl substituted in one or several positions with one or more compounds selected from the group comprising fluoride, chloride, hydroxy, C₁-C₄ alkoxy, C₁-C₄ alkylthio, C₂-C₅ acyloxy or C₁-C₄ alkyl, and wherein R2 represents hydrogen or C₁-C₄ alkyl, and wherein n is an integer from 1 to 12, and wherein i is an odd number and indicates the position relative to COOR₂, and wherein X_i independent of each other are selected from the group comprising O, S, SO, SO₂, Se and CH₂, and with the proviso that at least one of the X_i is not CH₂, and or a salt, prodrug or complex thereof is used in the treatment and/or prevention of primary and secondary metastatic neoplasms.

Claims

1. A method of inhibiting the metastasis of metastatic neoplasms comprising the administration to a mammal in need thereof an effective amount of a fatty acid analogue having the following formula

R₁-[x_i-CH₂]_n—

COOR₂

wherein R₁ is;

a C₂-C₂₄ alkene with one or more double bonds and/or with one or more triple bonds; and

/or

a C₂-C₂₄ alkyne, and/or

a C₁-C₂₄ alkyl, or a C₁-C₂₄ alkyl substituted in one or several positions with one a more compounds selected from the group comprising fluoride, chloride, hydroxy, C₁-C₄ alkoxy, C₁-C₄ alkylthio, C₂-C₅ acyloxy or C₁-C₄ alkyl, and

wherein R₂ represents hydrogen or C₁-C₄ alkyl, and

wherein n is an integer from 2-12, and

wherein i is an odd number and indicates the position relative to COOR₂, and

wherein x_i are independently selected from the group consisting of O, S, SO, SO₂, Se and CH₂, and

with the proviso that at least one of the x_i is not CH₂; and

with the proviso that if R₁ is an alkyl, then x_i=3 is not Se or S;

a salt, prodrug or complex thereof, wherein said metastatic neoplasms are sensitive to the effects of said fatty acid analogue.

2. A method as set forth in claim 1, wherein the method is effective to inhibit the invasion of a primary tumor into connective tissue.

3. A method as set forth in claim 1, wherein the method is effective to inhibit the formation of a secondary tumor.

4. A method as set forth in claim 1, wherein the method is effective to increase the survival of a mammal with a tumor due to decrease in the survival-threatening effects of the tumor.

5. A method as set forth in claim 1, wherein the method is effective to maintain a therapeutically effective concentration substantially continuously in the blood of the mammal during the period of administration.

6. A method as set forth in claim 1, wherein the fatty acid analogue is administered in unit dosage forms.

7. A method of treating the metastasis of metastatic neoplasms comprising the administration to a mammal in need thereof an effective amount of a fatty acid analogue having the following formula

R₁-[x_i-CH₂]_n—

COOR₂

wherein R₁ is;

a C₂-C₂₄ alkene with one or more double bonds and/or with one a more triple bonds, end/or

C₂-C₂₄ alkyne, and/or

C₁-C₂₄ alkyl, or a C₁-C₂₄ alkyl substituted in one or several positions with one or more compounds selected from the group comprising fluoride, chloride, hydroxy, C₁-C₄ alkoxy, C₂-C₄ alkyltliio, C₂-C₅ acyloxy or C₁-C₄ alkyl, and

wherein R₂ represents hydrogen or C₁-C₄ alkyl, and

wherein n is an integer from 1-12, and

wherein i is an odd number and indicates the position relative to COOR₂, and

wherein x_i are independently selected from the group consisting of O , S, SO, SO₂, Se and CH₂, and

with the proviso that at least one of the x₁ is not CR₂;

a salt, prodrug or complex thereof, wherein said metastatic neoplasms are sensitive to the effects of said fatty acid analogue.

8. A method as set forth in claim 7, wherein the fatty acid analogue is tetradecylthioacetic acid.

9. A method as set forth in claim 7, wherein the fatty acid analogue is tetradecylselenoacetic acid.

10. A method as set forth in claim 7, wherein the treatment is effective to inhibit the invasion of a primary tumor into connective tissue.

11. A method as set forth in claim 7, herein the treatment is effective to inhibit the formation of a secondary tumor.

12. A method as set forth in claim 7, wherein the treatment is effective to increase the survival of a mammal with a tumor due to decrease in the survival-threatening effects of the tumor.

13. A method as set forth in claim 7, wherein the treatment is effective to maintain a therapeutically effective concentration substantially continuously in the blood of the mammal during the period of administration.

14. A method as set forth in claim 7, wherein the fatty acid analogue is administered in unit dosage forms.

15. A method of inhibiting the metastasis of metastatic neoplasms comprising the administration to a mammal in need thereof an effective amount of a fatty acid analogue having the following formula

R₁-x-CH₂—

COOR₂

wherein R₁ is;

a C₁-C₂₄ alkyl, and

wherein R₂ represents hydrogen or C₁-C₄ alkyl, and

wherein x is independently selected from the group consisting of S and Se;

a salt, prodrug or complex thereof, wherein said metastatic neoplasms are sensitive to the effects of said fatty acid analogue.

16. The method as set forth in claim 15, wherein the fatty acid analogue is tetradecylthioacetic acid.

17. The method as set forth in claim 15, wherein the fatty acid analogue is tetradecylselenoacetic acid.

18. The method as set forth in claim 15, wherein the method is effective to inhibit the invasion of a primary tumor into connective tissue.

19. The method as set forth in claim 15, wherein the method is effective to inhibit the formation of a secondary tumor.

20. The method as set forth in claim 15, wherein the method is effective to increase the survival of a mammal with a tumor due to decrease in the survival-threatening effects of the tumor.

21. The method as set forth in claim 15, wherein the method is effective to maintain a therapeutically effective concentration substantially continuously in the blood of the mammal during the period of administration.

22. The method as set forth in claim 15, wherein the fatty acid analogue is administered in unit dosage forms.