Melampomagnolide B derivatives

Patent metadata

Field	Value
Publication number	US-9469650-B2
Application number	US-201414537389-A
Country	US
Kind code	B2
Filing date	Nov 10, 2014
Priority date	Nov 8, 2013
Publication date	Oct 18, 2016
Grant date	Oct 18, 2016

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 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 .

2. The compound 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 compound 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, dimethylaminoethoxy, piperdinylpropoxy, piperdinylethoxy, pyrrolidinylethoxy, morpholinylethyoxy, piperidinylethoxyhydroxyethylthio, and piperdinylethyl.

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

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

6. The compound 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. A pharmaceutically acceptable salt comprising a compound of claim 1 .

Assignees

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

Inventors

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

Classifications

• C07D493/04 Primary

  Ortho-condensed systems · CPC title