Synthesis of anti-estrogenic and other therapeutic steroids from 21-hydroxy-19-norpregna-4-en-3-one
AssigneeSRI International
InventorsRichard H. Peters, Jyanwei Liu, John G. Johansson, Kenneth J. Ryan, Wan-Ru Chao, Masato Tanabe
Life of this patent
Estimating the term…
Abstract
Syntheses of steroids such as 3-hydroxy-7α-methyl-21-[2′-methoxy-4′-(diethylaminomethyl)-phenoxy]-19-norpregna-1,3,5(10)triene citrate (“SR 16234”) and analogs thereof are provided, wherein 21-hydroxy-19-norpregna-4-en-3-one serves as a starting material or intermediate. The latter compound may be readily prepared from estrone-3-methyl ether. Certain intermediates in these syntheses also have value as therapeutic agents, for example in the treatment of prostate disorders such as prostatic cancer.
Claims7
A compound having the structural formula (V)
- wherein:
- R1 is hydrogen or CR11R12, wherein R11 and R12 are hydrogen or lower alkyl;
- R2 is selected from the group consisting of hydrogen, hydroxyl, alkyl, —OR13, and —SR13 wherein R13 is alkyl;
- R3 is hydrocarbyl;
- R4, R5, and R7 are independently selected from the group consisting of hydrogen and lower alkyl;
- R6Mod is selected from the group consisting of hydrogen, alkyl, acyl, —C(O)-aryl, —C(O)-alkyl, hydroxyl-protecting groups, and hydroxyl-activating groups;
- R8a is oxo;
- R9 is hydrogen or alkyl;
- R10 is methyl or ethyl;
- and
- R20 is hydroxyl, hydroxymethyl, protected hydroxyl, protected hydroxymethyl, activated hydroxyl, activated hydroxymethyl, or
- in which m is zero or 1, p is an integer in the range of 1 to 7, R21 and R22 are lower alkyl or are linked together to form a five- or six-membered heterocycloalkyl ring;
- and
- Q1, Q2, Q3, and Q4 are independently selected from the group consisting of hydrogen, hydroxyl, carboxyl, alkoxy, alkyl, halogen, amino, and alkyl-substituted amino.
A compound having the structural formula (VII)
- wherein:
- R3 is hydrogen or hydrocarbyl;
- R6Mod is selected from the group consisting of hydrogen, alkyl, acyl, —C(O)-aryl, and —C(O)-alkyl, hydroxyl-protecting groups, and hydroxyl-activating groups;
- R8b is oxo;
- m is zero or 1;
- p is an integer in the range of 1 to 7;
- R21 and R22 are lower alkyl or are linked together to form a five- or six-membered heterocycloalkyl ring;
- and
- Q1, Q2, Q3, and Q4 are independently selected from the group consisting of hydrogen, hydroxyl, carboxyl, alkoxy, alkyl, halogen, amino, and alkyl-substituted amino.
Dependencies are inferred from the claim text.