Reversible infertility in male mice following oral administration of alkylated imino sugars: a non-hormonal approach to male contraception

A method of reversibly rendering a fertile male mammal infertile, comprising the steps of:

• (a) administering to said mammal a pharmaceutical composition comprising one or more pharmaceutically acceptable excipients and a therapeutically effective amount of a compound of formula I or II, or a stereoisomer, pharmaceutically acceptable salt, or solvate thereof:
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• wherein each of R11, R11′, R12, R12′, R13, R13′, R14, R14′, R15, R15′, R31, R31′, R32, R32′, R33, R33′, R34, and R34′ is selected, independently from each other, from the group consisting of —H;
• —OH;
• —F;
• —Cl;
• —Br;
• —I;
• —NH2;
• alkyl- and dialkylamino;
• linear or branched C1-6 alkyl, C2-6 alkenyl and alkynyl;
• aralkyl;
• linear or branched C1-6 alkoxy;
• aryloxy;
• aralkoxy;
• -(alkylene)oxy(alkyl);
• —CN, —NO2, —COOH, —COO(alkyl);
• —COO(aryl);
• —C(O)NH(C1-6 alkyl);
• —C(O)NH(aryl);
• sulfonyl;
• (C1-6 alkyl)sulfonyl;
• arylsulfonyl;
• sulfamoyl, (C1-6 alkyl)sulfamoyl;
• (C1-6 alkyl)thio;
• (C1-6 alkyl)sulfonamide;
• arylsulfonamide;
• —NHNH2;
• —NHOH;
• aryl, and heteroaryl;
• wherein each alkyl, alkenyl, alkynyl, aryl, and heteroaryl moiety may be optionally substituted with one or more groups independently selected from the group consisting of —OH;
• —F;
• —Cl;
• —Br;
• —I;
• —NH2;
• alkyl- and dialkylamino;
• linear or branched C1-6 alkyl, C2-6 alkenyl and alkynyl;
• aralkyl;
• linear or branched C1-6 alkoxy, aryloxy;
• aralkoxy;
• -(alkylene)oxy(alkyl);
• —CN, —NO2, —COOH, —COO(alkyl);
• —COO(aryl);
• —C(O)NH(C1-6 alkyl);
• —C(O)NH(aryl);
• sulfonyl;
• (C1-6 alkyl)sulfonyl;
• arylsulfonyl;
• sulfamoyl, (C1-6 alkyl)sulfamoyl;
• (C1-6 alkyl)thio;
• (C1-6 alkyl)sulfonamide;
• arylsulfonamide;
• —NHNH2;
• and —NHOH;
• R2 and R4 are substituents selected independently of each other from the group consisting of linear or branched C1-18 alkyl, C2-18 alkenyl and alkynyl;
• and aralkyl,
• wherein each alkyl, alkenyl, alkynyl, and aryl moiety may be optionally substituted with one or more groups independently selected from the group consisting of —OH;
• —F;
• —Cl;
• —Br;
• —I;
• —NH2;
• alkyl- and dialkylamino;
• linear or branched C1-6 alkyl, C2-6 alkenyl and alkynyl;
• aralkyl;
• linear or branched C1-6 alkoxy, aryloxy;
• aralkoxy;
• —CN, —NO2, —COOH, —COO(alkyl);
• —COO(aryl);
• —C(O)NH(C1-6 alkyl);
• —C(O)NH(aryl);
• sulfonyl;
• (C1-6 alkyl)sulfonyl;
• arylsulfonyl;
• sulfamoyl, (C1-6 alkyl)sulfamoyl;
• (C1-6 alkyl)thio;
• (C1-6 alkyl)sulfonamide;
• arylsulfonamide;
• —NHNH2;
• and —NHOH;
• said composition being administered in an amount and for a time sufficient to render said male mammal infertile;
• and
• (b) cease administering said composition to said mammal, whereby said mammal is rendered fertile;
• and
• (c) repeating steps (a) and (b) one or more times.