Melampomagnolide B derivatives

Patent metadata

Field	Value
Publication number	US-9908892-B2
Application number	US-201615254849-A
Country	US
Kind code	B2
Filing date	Sep 1, 2016
Priority date	Nov 8, 2013
Publication date	Mar 6, 2018
Grant date	Mar 6, 2018

Abstract

The present disclosure provides derivatives of melampomagnolide B (MMB), including carbonates, carbamates, and thiocarbamates. The derivatives may be synthesized via an MMB triazole intermediate. These derivatives are useful for treating cancer in humans.

First claim

What is claimed is:

1. 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 (II), or a salt thereof, effective to inhibit growth of the cancer cell, the compound comprising Formula (I) or (II):

wherein:
X is O or S;
R 1 and R 2 are independently selected from the group consisting of —OR 3 , —O-alkyl-NR 3 R 4 , —SR 3 , —S-alkyl-NR 3 R 4 , alkyl-C(O)NR 3 R 4 , and -alkyl-R 5 or when X is S, R 1 is NR 3 R 4 ;
R 3 is selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, and R 5 ;
R 4 is selected from the group consisting of hydrogen, hydrocarbyl, and substituted hydrocarbyl;
R 5 is an optionally substituted nitrogen-containing heterocyclic ring;
one or more of R 3 and R 4 may form part of a ring or ring system chosen from the group consisting of heterocyclic, substituted heterocyclic, and combinations thereof; and
when R 4 is hydrogen, R 3 is selected from the group consisting of alkyl, R 5 , and substituted hydrocarbyl having at least one hydroxyl or R 5 ;
wherein the cancer cell is an acute myelogenous leukemia (AML) cancer cell or a solid tumor cell; and
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.

2. The method of claim 1 , wherein R 1 and R 2 are selected from the group consisting of alkoxy, alkylamino, dialkylamino, dialkylaminoalkoxy, heterocyclylalkoxy, hydroxyalkylamino, heterocycylamino, and heterocycylalkylamino.

3. The method of claim 2 , wherein R 1 and R 2 are selected from the group consisting of methylamino, dimethylamino, hydroxyhexylamino, hydroxyethylamino, pyrrolyl, pyrrolidinyl, pyridinyl, piperdinyl, pyrazinyl, piperazinyl, pyrimidinyl, imidazolyl, triazolyl, hydroxypiperdinyl, difluoropiperdinyl, triazolylamino, methylthiotriazolylamino, morpholinyl, morpholinylethylamino, pyridinylmethylamino, piperdinylethylamino, pyridinylethylamino, morpholinylpropylamino, imidiazolylpropylamino, methoxy, di methylaminoethoxy, piperdinylpropoxy, piperdinylethoxy, pyrrolidinylethoxy, morpholinylethyoxy, piperidinylethoxyhydroxyethylthio, and piperdinylethyl.

4. The method of claim 2 , wherein R 1 and R 2 are independently selected from the group consisting of imidazolylpropylaminocarbonylethylcarbonyl, difluoropiperinylcarbonylethylcarbonyl, methylthiotriazolylaminocarbonylethylcarbonyl, chloropyridinylmethylaminocarbonylethylcarbonyl, methylpiperdinylcarbonylethylcarbonyl, and methylpiperazinylcarbonylethylcarbonyl.

5. The method of claim 1 , wherein R 1 is R 5 , and R 2 is dialkylamino.

6. The method of claim 1 , wherein one or more R 1 , R 2 , R 3 , R 4 , or R 5 is substituted with at least one selected from the group consisting of methyl, ethyl, propyl, cyano, C 1 -C 3 -alkylamino, carboxyl, hydroxyl, trifluoromethyl, thio, alkylthio, and halogen.

7. The method of claim 1 , wherein the cancer cell is in vivo or in vitro.

Assignees

• Janganati Venumadhav
• Penthala Narsimha Reddy
• Crooks Peter A
• Jordan Craig T
• Bioventures Llc

Inventors

• Janganati Venumadhav
• Penthala Narsimha Reddy
• Crooks Peter A
• Jordan Craig T

Classifications

• C07D493/04 Primary

  Ortho-condensed systems · CPC title