SKIN CANCER TREATMENT

• US 20170119694A1
• Filed: 05/26/2015
• Published: 05/04/2017
• Est. Priority Date: 05/27/2014
• Status: Active Grant

• Current Assignee: Avexxin AS
• Original Assignee: Avexxin AS
• Inventors: Johansen, Berit, Feuerherm, Astrid Jullumistro
• Granted Patent: US 10,085,953 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/121 acyclic
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

A compound of formula (I)

R-L-CO—X  (I)

• • wherein R is a C_10-24 unsaturated hydrocarbon group optionally interrupted by one or more heteroatoms or groups of heteroatoms selected from S, O, N, SO, SO₂, said hydrocarbon group comprising at least 4 non-conjugated double bonds;
  • L is a linking group forming a bridge of 1 to 5 atoms between the R group and the carbonyl CO wherein L comprises at least one heteroatom in the backbone of the linking group; and
  • X is an electron withdrawing group or a salt thereof
  • for use in the treatment of skin cancer such as basal cell carcinoma.

Claims

1-18. -18. (canceled)

19. A method of treating skin cancer comprising administering to an animal in need thereof an effective amount of a compound of formula (I):

R-L-CO—

X 

 

(I)

wherein R is a C_10-24 unsaturated hydrocarbon group optionally interrupted by one or more heteroatoms or groups of heteroatoms selected from S, O, N, SO, SO₂, said hydrocarbon group comprising at least 4 non-conjugated double bonds;

L is a linking group forming a bridge of 1 to 5 atoms between the R group and the carbonyl CO wherein L comprises at least one heteroatom in the backbone of the linking group; and

X is an electron withdrawing group;

or a salt thereof.

20. The method of claim 19 wherein said hydrocarbon group R has 5 to 7 double bonds.

21. The method of claim 19 wherein in said hydrocarbon group R no double bond is conjugated with the carbonyl group.

22. The method of claim 19 wherein in said hydrocarbon group R all double bonds are in the cis configuration or wherein in said hydrocarbon group all double bonds are in the cis configuration except the double bond nearest the carbonyl.

23. The method of claim 19 wherein the R group comprises 17 to 19 carbon atoms.

24. The method of claim 19 wherein linking group L comprises —

CH₂—

, —

CH(C_1-6alkyl)-, —

N(C_1-6alkyl)-, —

NH—

, —

S—

, —

O—

, —

CH═

CH—

, —

CO—

, —

SO—

, or —

SO₂—

which can be combined with each other in any (chemically meaningful) order to form the linking group.

25. The method of claim 19 wherein L comprises at least one heteroatom or group of heteroatoms in the backbone of the linking group selected from O, S, N, or SO.

26. The method of claim 19 wherein L is —

NH₂CH₂, —

NH(Me)CH₂—

, —

SCH₂—

, and —

SOCH₂—

.

27. The method of claim 19 wherein X is O—

C_1-6 alkyl, CN, OCO₂—

C_1-6 alkyl, phenyl, CHal₃, CHal₂H, CHalH₂ wherein Hal represents a halogen.

28. The method of claim 27 wherein Hal is fluorine.

29. The method of claim 27 wherein X is CHal₃.

30. The method of claim 27 wherein X is CF₃.

31. The method of claim 19 wherein R is a linear unsubstituted C_10-24 unsaturated hydrocarbon group said hydrocarbon group comprising at least 4 non-conjugated double bonds.

32. The method of claim 19 wherein said compound of formula (I) has the formula:

33. The method of claim 32 is CF₃.

34. The method of claim 19 wherein said compound has the formula (I′

)

R—

Y1-Y2-CO—

X 

 

(I′

)

wherein R and X are as hereinbefore defined;

Y1 is selected from O, S, NH, N(C_1-6-alkyl), SO or SO₂ and

Y2 is (CH₂)_n or CH(C_1-6 alkyl);

or

where n is 1 to 3.

35. The method of claim 19 wherein the compound of formula (I) is AVX001 or AVX002.

36. The method of claim 19 wherein the skin cancer is squamous cell carcinoma or basal cell carcinoma.

37. The method of claim 19 wherein the animal has squamous cell carcinoma or basal cell carcinoma.

38. The method of claim 19 wherein the compound is administered orally or topically.

39. The method of claim 19 wherein the animal is a mammal.

40. The method of claim 19 wherein the animal is a human.