Chiral Diacylhydrazine Ligands for Modulating the Expression of Exogenous Genes via an Ecdysone Receptor Complex
AssigneeIntrexon Corporation
InventorsRobert Eugene Hormann, Bing Li
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Abstract
The present invention provides diacylhydrazine ligands and chiral diacylhydrazine ligands for use with ecdysone receptor-based inducible gene expression systems. Thus, the present invention is useful for applications such as gene therapy, large scale production of proteins and antibodies, cell-based screening assays, functional genomics, proteomics, metabolomics, and regulation of traits in transgenic organisms, where control of gene expression levels is desirable. An advantage of the present invention is that it provides a means to regulate gene expression and to tailor expression levels to suit the user's requirements.
Claims19
1-25. (canceled)
A process for preparing
- (1) an enantiomerically enriched compound having Formula II:
- wherein:
- A is alkoxy, arylalkyloxy, aryloxy, arylalkyl, optionally substituted aryl or optionally substituted heteroaryl;
- B is optionally substituted aryl or optionally substituted heteroaryl;
- and
- R1 and R2 are independently optionally substituted alkyl, arylalkyl, hydroxyalkyl, haloalkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heterocycle, optionally substituted aryl or optionally substituted heteroaryl;
- with the proviso that R1 does not equal R2;
- wherein the absolute configuration at the asymmetric carbon atom bearing R1 and R2 is predominantly S;
- or
- (2) an enantiomerically enriched compound of Formula III:
- wherein:
- A is alkoxy, arylalkyloxy, aryloxy, arylalkyl, optionally substituted aryl or optionally substituted heteroaryl;
- B is optionally substituted aryl or optionally substituted heteroaryl;
- and
- R1 and R2 are independently optionally substituted alkyl, arylalkyl, hydroxyalkyl, haloalkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heterocycle, optionally substituted aryl or optionally substituted heteroaryl;
- with the proviso that R1 does not equal R2;
- wherein the absolute configuration at the asymmetric carbon atom bearing R1 and R2 is predominantly R, comprising:
- a) reacting an acyl hydrazine of Formula XI
- with a ketone of Formula XII
- to form a compound of Formula XIII;
- wherein R1 does not equal R2;
- b) reducing the compound of Formula XIII in the presence of a chiral catalyst to form a compound of Formula S-XIV or R-XIV;
- and
- c) reacting the compound of Formula S-XIV or R-XIV with a compound of formula B-CO-LG where LG is a leaving group to form the compound of Formula II or Formula III.
30-47. (canceled)
Dependencies are inferred from the claim text.