METHOD OF MAKING AND USING 7alpha,11beta-DIMETHYL-17beta-HYDROXYESTR-4-EN-3-ONE 17-UNDECANOATE
AssigneesGovernment of the United States of America, represented by the Secretary, Department of Health, Human Services
InventorsRichard P. Blye, Hyun K. Kim
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Abstract
Methods of using 7α,11β-dimethyl-17β-hydroxy-4-estren-3-one bucyclate (I) and 7α,11β-dimethyl-17β-hydroxyestr-4-en-3-one 17-undecanoate (II) for various hormonal therapies, dosage forms comprising 7α,11β-dimethyl-17β-hydroxy-4-estren-3-one bucyclate and 7α,11β-dimethyl-17β-hydroxyestr-4-en-3-one 17-undecanoate, and processes for their preparation.
Claims48
1-38. (canceled)
A crystalline compound of formula 10
- having a melting point of 155-157° C.
A compound of formula 5
A compound of formula 6
A compound of formula 7
A compound of formula 9
44-45. (canceled)
A method for providing hormonal therapy to a patient comprising the oral administration of up to about 75 mg/day of 7α,11β-dimethyl-17β-hydroxyestr-4-en-3-one 17-undecanoate to a patient in need thereof.
A method for providing hormonal therapy to a patient comprising administering parenterally to the patient an average dosage of up to about 600 mg/month of 7α,11β-dimethyl-17β-hydroxyestr-4-en-3-one 17-undecanoate during the treatment period.
An oral dosage formulation comprising 7α,11β-dimethyl-17β-hydroxyestr-4-en-3-one 17-undecanoate and a pharmaceutically-acceptable carrier.
An aqueous formulation for parenteral administration comprising 7α,11β-dimethyl-17β-hydroxyestr-4-en-3-one 17-undecanoate and water.
A method for preparing 7α,11β-dimethyl-17β-hydroxyestr-4-en-3-one 17-undecanoate (Compound II) comprising the steps of:
- (a) converting the ether group of Compound 1
- to a carbonyl group, providing Compound 2
- (b) reducing the carbonyl group at C17 and ketalizing the carbonyl group at C3 of Compound 2 to provide Compound 4;
- (c) epoxidizing Compound 4 to provide the epoxide of Compound 5;
- (d) opening the epoxide ring in Compound 5 and substituting an alkyl group at C11 to provide Compound 6 (comprising a mixture of 11α- and 11β-methyl isomers, Compounds 6a and 6b, respectively) by use of a Grignard reagent;
- (e) deketalizing and dehydrating Compound 6 to provide Compound 7;
- (f) converting Compound 7a to Compound 9;
- (g) converting Compound 9 to Compound 10;
- and
- (h) esterifying Compound 10 to provide Compound II
7α,11β-dimethyl-17β-hydroxyestr-4-en-3-one 17-undecanoate (Compound II) in crystalline form.
Dependencies are inferred from the claim text.