Melampomagnolide b derivatives

Patent metadata

Field	Value
Publication number	US-2016368928-A1
Application number	US-201615251889-A
Country	US
Kind code	A1
Filing date	Aug 30, 2016
Priority date	Nov 8, 2013
Publication date	Dec 22, 2016
Grant date	—

Abstract

The present disclosure provides derivatives of melampomagnolide B (MMB), including carbonates, carbamates, thiocarbamates, ester and amide derivatives of MMB. These derivatives are useful for treating cancer in humans.

First claim

What is claimed is:

1 . A process for preparing a compound comprising Formula (I), the process comprising:
a) contacting a compound comprising MMB with a compound selected from the group consisting of:
(i) a compound comprising a carboxylic acid; and
(ii) a compound comprising an acyl chloride; or
b) contacting a compound comprising melampomagnolic acid with a compound comprising a heterocyclic amine; or c) contacting a compound comprising an amine derivative of MMB with a compound comprising a carboxylic acid to form a compound comprising Formula (I):

wherein:
R is selected from the group consisting of

wherein:
R 1 is selected from the group consisting of substituted indoles, substituted heterocyclic aromatic, and substituted aromatic derivatives;
R 2 is selected from the group consisting of substituted indoles; and
R 3 is selected from the group consisting of substituted amines.

2 . The process of claim 1 , wherein prior to step (a), an ester may be converted into the compound comprising a carboxylic acid prior to contacting with a compound comprising MMB.

3 . The process of claim 1 , wherein prior to step (a), a compound may be converted into the compound comprising an acyl chloride prior to contacting with a compound comprising MMB.

4 . The process of claim 1 , wherein the compound comprising a carboxylic acid is be selected from the group consisting of a simple and substituted indole, a benzothiophene, a benzofuran carboxylic acid, and a heterocyclic carboxylic acid.

5 . The process of claim 1 , wherein the compound comprising a carboxylic acid is selected from the group consisting of 5-methoxyindole-2-carboxylic acid, 5-chloro-indole-2-carboxylic acid, 5-fluorindole-2-carboxylic acid, indole-3-acetic acid, indole-3-acrylic acid, indomethacin, benzothiophene-2-carboxylic acid, 3-chlorobenzothiopene-2-carboxylic acid, benzofuran-2-carboxylic acid, 2-aminonicotinic acid, pyrazine-2-carboxylic acid, 5-methylthiophene-2-carboxylic acid, acetic acid, 5-(2-oxohexahydro-1H-thienol[3,4-d]imidazol-4-yl)pentanoic acid, and 12-(5-(2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentan-amido)dodecanoic acid.

6 . The process of claim 1 , wherein the compound comprising an acyl chloride is selected from the group consisting of a substituted benzoyl or napthoyl chloride.

7 . The process of claim 1 , wherein the compound comprising an acyl chloride is selected from the group consisting of substituted 2-(1H-indol-3-yl)-2-oxoacetyl chlorides.

8 . The process of claim 1 , wherein the compound comprising a heterocyclic amine is selected from the group consisting of imidazole, benzimidazole, morpholine, piperidine, pyrrole, pyrrolidine, triazole, tetrazole, piperazine, pyridine, pyrazoloimidazole, methanol, ethanol, N,N-dimethylethanolamine, morpholinoethanol, and piperidinopropanol.

9 . A method for inhibiting growth of a cancer cell, the method comprising contacting the cancer cell with an amount of a compound comprising Formula (I), or a salt thereof, effective to inhibit growth of the cancer cell, the compound comprising Formula (I):

wherein:
R is selected from the group consisting of

wherein:
R 1 is selected from the group consisting of substituted indoles, substituted heterocyclic aromatic, and substituted aromatic derivatives;
R 2 is selected from the group consisting of substituted indoles; and
R 3 is selected from the group consisting of substituted amines.

10 . The method of claim 9 , wherein Formula (I) comprises:

wherein:
X is selected from the group consisting of S, O, NH, NR 10 ;
R 9 is selected from the group consisting of OMe, Cl, Br and F; and
R 10 is selected from the group consisting of H, CH 3 , benzyl, substituted benzyl, benzoyl, substituted benzoyl, and benzylsulfonyl and substituted benzylsulfonyl.

11 . The method of claim 9 , wherein Formula (I) comprises:

wherein:
R 11 is selected from the group consisting of H, CH 3 , benzyl, substituted benzyl, benzoyl, substituted benzoyl, and benzylsulfonyl and substituted benzylsulfonyl; and
R 12 and R 13 are independently selected from the group consisting of H, F, Cl, Br, OCH 3 , CN, CH 3 , NO 2 and COOCH 3 .

12 . The method of claim 9 , wherein Formula (I) comprises:

wherein:
R 14 is selected from the group consisting of 2-thiophenyl, 3-thiophenyl, 2-pyrazine, 3-pyrazine, 2-amino nicotinic acid, indole-3-acetic acid, indole-3-acrylic acid.

13 . The method of claim 9 , wherein Formula (I) comprises:

wherein:
R 15 is selected from the group consisting of:

14 . The method of claim 9 , wherein Formula (I) comprises:

wherein:
R 1 is selected from the group consisting of substituted indoles, substituted heterocyclic aromatic, aromatic and aliphatic derivatives.

15 . The method of claim 9 , wherein the cancer cell is in vivo or in vitro.

16 . The method of claim 9 , wherein the cancer cell is a leukemia cancer cell.

17 . The method of claim 16 , wherein the leukemia cancer cell is an acute myelogenous leukemia (AML) cancer cell.

18 . The method of claim 9 , wherein the cancer cell is a solid tumor cell.

19 . The method of claim 18 , wherein the solid tumor cell is selected from the group consisting of non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer and breast cancer.

Assignees

• Univ Arkansas
• Univ Colorado Regents

Inventors

• Bommagani Shobanbabu
• Crooks Peter
• Penthala Narsimha Reddy
• Janganati Venumadhav
• Jordan Craig T
• Ponder Jessica

Classifications

• C07D493/04 Primary

  Ortho-condensed systems · CPC title