Structural modification of 19-norprogesterone I: 17-α-substituted-11-β-substituted-4-aryl and 21-substituted 19-norpregnadienedione as new antiprogestational agents

A compound of general formula I:

• wherein:
• R1 is a member selected from the group consisting of —CHO, —CH(OH)CH3, and —C(O)CH3;
• R2 is —OC(O)R6 and R6 is a member selected from the group consisting of —CH2CH3, —CH2OCH3 and —OCH3;
• R3 is a member selected from the group consisting of alkyl, substituted alkyl, alkoxy and acyloxy;
• R4 is a member selected from the group consisting of hydrogen and alkyl;
• X is a member selected from the group consisting of ═O and ═N—OR5, wherein R5 is a member selected from the group consisting of hydrogen and alkyl;
• wherein the term “alkyl” refers to a saturated monovalent hydrocarbon radical of 1-12 carbon atoms;
• and
• with the proviso that if R6 is —CH2CH3 and R1 is —CHO or —C(O)CH3, then R3 is other than C1-4 alkyl or —OC(O)C1-6 alkyl.

A compound of the general formula I:

• wherein:
• R1 is a member selected from the group consisting of —CHO, —CH(OH)CH3, and —C(O)CH3;
• R2 is —OC(O)R6 wherein R6 is alkyl or alkoxyalkyl;
• R3 is a member selected from the group consisting of alkyl, substituted alkyl, alkoxy and acyloxy;
• R4 is a member selected from the group consisting of hydrogen and alkyl;
• X is a member selected from the group consisting of ═O and ═N—OR5, wherein R5 is a member selected from the group consisting of hydrogen and alkyl;
• wherein the term “alkyl” refers to a saturated monovalent hydrocarbon radical of 1-12 carbon atoms;
• and
• with the proviso that if R6 is alkyl and R1 is —CHO or —C(O)CH3, then R3 is other than C1-4 alkyl or —OC(O)C1-6 alkyl.

A compound of the general formula:

• wherein:
• R1 is a member selected from the group consisting of —OCH3, —SCH3, —CHO, —CH(OH)CH3 and —C(O)CH3;
• R2 is a member selected from the group consisting of alkoxy, SAc, vinyloxy, —SCN, and —OC(O)R6, wherein R6 is a member selected from the group consisting of alkyl, substituted alkyl, alkoxyalkyl, alkoxy, vinyloxy and ethynyloxy;
• R3 is selected from the group consisting of methoxymethoxy, methoxyethoxy, aryloxy, arylalkoxy, and acyloxy;
• R4 is a member selected from the group consisting of hydrogen and alkyl;
• and
• X is a member selected from the group consisting of ═O and ═N—OR5, wherein R5 is a member selected from the group consisting of hydrogen and alkyl;
• wherein the term “alkyl” refers to a saturated monovalent hydrocarbon radical of 1-12 carbon atoms;
• and
• with the proviso that if R2 is —OC(O)R6, wherein R6 is alkyl, and R1 is —CHO or —C(O)CH3, then R3 is other than —OC(O)C1-6 alkyl.

A compound of the general formula:

• wherein:
• R1 is —C(O)CH3:
• R2 is a member selected from the group consisting of —SAc, alkoxy, vinyloxy, —SCN, and —OC(O)R6, wherein R6 is a member selected from the group consisting of alkyl, substituted alkyl, alkoxyalkyl, alkoxy, vinyloxy and ethynyloxy;
• R3 is a member selected from the group consisting of alkyl, substituted alkyl, alkoxy and acyloxy;
• R4 is a member selected from the group consisting of hydrogen and alkyl;
• and
• X is a member selected from the group consisting of ═O and ═N—OR5, wherein R5 is a member selected from the group consisting of hydrogen and alkyl;
• wherein the term “alkyl” refers to a saturated monovalent hydrocarbon radical of 1-12 carbon atoms;
• and
• with the proviso that if R2 is —OC(O)R6. wherein R6 is alkyl, then R3 is other than C1-4 alkyl or —OC(O)C1-6 alkyl.

A compound of the general formula:

• wherein:
• R1 is a member selected from the group consisting of —OCH3, —SCH3, —CHO, —CH(OH)CH3, and —C(O)CH3;
• R2 is —OC(O)R6, wherein R6 is a member selected from the group consisting of alkyl and alkoxyalkyl;
• R3 is a member selected from the group consisting of alkyl, substituted alkyl, alkoxy and acyloxy;
• R4 is a member selected from the group consisting of hydrogen and alkyl;
• and
• X is a member selected from the group consisting of ═O and ═N—OR5, wherein R5 is a member selected from the group consisting of hydrogen and alkyl;
• wherein the term “alkyl” refers to a saturated monovalent hydrocarbon radical of 1-12 carbon atoms;
• and
• with the proviso that if R2 is —OC(O)R6, wherein R6 is alkyl, and R1 is —CHO or —C(O)CH3, then R3 is other than C1-4 alkyl or —OC(O)C1-6 alkyl.