Aconitine compounds, compositions, uses, and preparation thereof
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsJustin Du Bois, Brian M. Andresen, Frederic Menard
Life of this patent
Estimating the term…
Abstract
Compound derivatives of aconitine are provided, in particular derivatives that modulate the activity of sodium channels. Also provided are pharmaceutical compositions comprising compounds of the invention and a pharmaceutically acceptable carrier. The subject compounds are useful in treatments, including treatments to modulate neuronal activity or to bring about muscular relaxation. The compounds also find use in the treatment of subjects suffering from a voltage-gated sodium channel-enhanced ailment or from pain. Further methods are provided for the preparation of the aconitine derivatives.
Claims41
A compound represented by structural formula (II):
- or a pharmaceutically acceptable salt or prodrug thereof, wherein:
- R is alkyl, alkenyl, alkynyl, alkoxy, alkylamino, aryl, aryloxy, arylamino, aralkoxy, aralkamino, heteroaryl, heteroaryloxy, heteroarylamino, heteroaralkyl, heteroaralkoxy, heteroaralkamino, cycloalkyl, cycloalkenyl, cycloalkoxy, cycloalkamino, heterocyclyl, heterocyclyloxy, heterocyclylamino, heterocyclylalky, heterocyclylalkoxy, or heterocyclylalkamino, and is optionally substituted with 1 to 3 A groups;
- R2 is alkyl, alkoxy, or,
- each R3 is independently hydrogen or a protecting group;
- each R4 is alkyl, alkenyl, alkynyl, alkoxy, alkylamino, aryl, aryloxy, arylamino, aralkoxy, aralkamino, heteroaryl, heteroaryloxy, heteroarylamino, heteroaralkyl, heteroaralkoxy, heteroaralkamino, cycloalkyl, cycloalkenyl, cycloalkoxy, cycloalkamino, heterocyclyl, heterocyclyloxy, heterocyclylamino, heterocyclylalky, heterocyclylalkoxy, or heterocyclylalkamino, and is optionally substituted with 1 to 3 A groups;
- each A is independently alkyl, alkenyl, alkynyl, alkoxy, alkanoyl, alkylamino, aryl, aryloxy, arylamino, aralkyl, aralkoxy, aralkanoyl, aralkamino, heteroaryl, heteroaryloxy, heteroarylamino, heteroaralkyl, heteroaralkoxy, heteroaralkanoyl, heteroaralkamino, cycloalkyl, cycloalkenyl, cycloalkoxy, cycloalkanoyl, cycloalkamino, heterocyclyl, heterocyclyloxy, heterocyclylamino, heterocyclylalky, heterocyclylalkoxy, heterocyclylalkanoyl, heterocyclylalkamino, hydroxyl, thio, amino, alkanoylamino, aroylamino, aralkanoylamino, alkylcarboxy, carbonate, carbamate, guanidinyl, urea, halo, trihalomethyl, cyano, nitro, phosphoryl, sulfonyl, sulfonamindo, or azido;
- and
- R5 is alkyl;
- provided that,
- when R is unsubstituted phenyl, R2 is
- and each R3 is hydrogen, then R4 is not alkyl or alkenyl;
- and
- when R is p-methoxyphenyl, R2 is
- and each R3 is hydrogen, then R4 is not methyl.
A method of preparing an aconitine derivative, comprising the step of:
- i) selectively protecting an aconitine congener at the C-3 and C-13 hydroxyl groups.
Dependencies are inferred from the claim text.