Estrogen receptor imaging agents
AssigneeNortheastern University
InventorsRobert N. Hanson, Kinh-Luan Dao
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Abstract
Compounds useful for molecular imaging of cells expressing estrogen receptors are provided. Also provided are intermediates for making the compounds and methods of making the compounds using a modular convergent strategy. Further, methods of making the intermediates are described, as well as methods of diagnosing disease in a subject by using the compounds as imaging agents.
Claims12
A compound according to formula (I)
- wherein n is a number in the range of 1-10;
- m is a number in the range of 4-10;
- R1 is H or a C1-3 alkyl group;
- and R2 is either absent, or selected from the group consisting of H and a C1-3 alkyl group.
A compound according to formula (II)
- wherein m is a number in the range of 4-10;
- and R1 is H or a C1-3 alkyl group;
- and R2 is either absent, or selected from the group consisting of H and a C1-3 alkyl group.
A compound according to formula (III)
- wherein m is a number in the range of 4-10;
- R1 is H or a C1-3 alkyl group;
- and R2 is either absent, or selected from the group consisting of H and a C, 1-3 alkyl group.
A process for the preparation of a compound according to formula (I) comprising the step of reacting a compound according to formula (II) with a compound according to formula (IV) using a Huisgen [3+2] cycloaddition reaction,
- wherein n is a number in the range of 1-10;
- m is a number in the range of 4-10;
- R1 is H or a C1-3 alkyl group;
- and R2 is either absent, or selected from the group consisting of H and a C1-3 alkyl group, and wherein x is a number in the range of 1-10.
A process for the preparation of a compound according to formula (XVIII)
- comprising the steps of transforming estra-5(10),9(11)-diene-3,17-dione 3-ethylenedioxy ketal (1) into 11β-(4-Hydroxy-phenyl)-estra-4,9-diene-3,17-dione (3) by reacting (1) initially with a peroxide reagent to give an epoxide, treating the product obtained with the Grignard reagent derived from trimethylsilyloxyphenyl bromide to obtain compound (3), alkylating (3) with dimethylaminoethyl chloride to obtain compound (4), aromatizing (4) with acetyl bromide and acetic anhydride to obtain compound (5), reducing and saponifying (5) to obtain compound (6), demethylating (6) with alpha chloroethyl chloroformate to obtain compound (7), and reacting (7) with reagent (8a),
- thereby obtaining the compound according to formula (XVIII).
A process for the preparation of a compound according to formula (XIX)
- comprising the steps of transforming estra-5(10),9(11)-diene-3,17-dione 3-ethylenedioxy ketal (1) into 11β-(4-Hydroxy-phenyl)-estra-4,9-diene-3,17-dione (3), by reacting (1) initially with a peroxide reagent to give an epoxide, treating the product obtained with the Grignard reagent derived from trimethylsilyloxyphenyl bromide to obtain compound (3), alkylating (3) with dimethylaminoethyl chloride to obtain compound (4), aromatizing (4) with acetyl bromide and acetic anhydride to obtain compound (5), reducing and saponifying (5) to obtain compound (6), demethylating (6) with alpha chloroethyl chloroformate to obtain compound (7), and reacting (7) with reagent (8b)
- thereby obtaining the compound according to formula (XIX).
A process for the preparation of a compound according to formula (XX)
- comprising the steps of:
- preparing 2-(4-bromophenoxy)-N,N-dimethylethanamine (1) by reacting 4-bromophenol with 2-dimethylaminoethyl chloride, converting (1) to (4-(2-(dimethylamino)ethoxy)phenyl)magnesium bromide (2) by treating with reagents comprising Mg, and iodine, and reacting (2) with 3,3-Ethylenedioxy-5(10)-α-epoxy-estr-9-ene-17-one (3) in the presence of CuI and acetic acid
- thereby obtaining the compound according to formula (XX).
Dependencies are inferred from the claim text.