Pyrazole compounds and piperazine compounds that are inhibitors of ALDH1A1 and ALDH1A2 and methods for using the pyrazole compounds and piperazine compounds in male contraceptive compositions for preventing spermatogenesis.

The present invention provides for compounds of formula (I)

##STR00001##

wherein A.sup.1, A.sup.2, A.sup.3, A.sup.4, X.sup.1, X.sup.2, Y.sup.1, L.sup.1, G.sup.1, R.sup.x, and R.sup.y have any of the values defined thereof in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cancer, and AIDS. Also provided are pharmaceutical compositions comprising one or more compounds of formula (I).

The present invention provides bivalent inhibitors of BET bromodomains, such as compounds of Formulae (I), (II), (III), (IV), (V), and (VI). Some bromodomain-containing proteins (e.g., BRD4) have a tandem bromodomain primary structure comprising more than one bromodomain binding site (e.g., BRD4 comprises BD1 and BD2). Bivalent inhibitors of BET bromodomains provided herein can target bromodomains through advantageous multivalent interactions, and can therefore can be to treat diseases or conditions associated with bromodomain-containing proteins. The present also provides pharmaceutical compositions and kits comprising the inventive compounds, as well as methods of using the inventive compounds.

##STR00001##

The present invention provides bivalent inhibitors of BET bromodomains, such as compounds of Formulae (I), (II), (III), (IV), (V), and (VI). Some bromodomain-containing proteins (e.g., BRD4) have a tandem bromodomain primary structure comprising more than one bromodomain binding site (e.g., BRD4 comprises BD1 and BD2). Bivalent inhibitors of BET bromodomains provided herein can target bromodomains through advantageous multivalent interactions, and can therefore can be to treat diseases or conditions associated with bromodomain-containing proteins. The present also provides pharmaceutical compositions and kits comprising the inventive compounds, as well as methods of using the inventive compounds.

##STR00001##

The invention relates to substituted bicyclic compounds, which are useful for inhibition of BET protein function by binding to bromodomains, pharmaceutical compositions comprising these compounds, and use of the compounds and compositions in therapy.

The present disclosure relates to inhibitors of mitochondrial function. Methods of screening compounds for mitochondrial inhibition are disclosed. Also described are methods of using mitochondrial inhibitors called mitoriboscins—mitochondrial-based therapeutic compounds having anti-cancer and antibiotic properties—to prevent or treat cancer, bacterial infections, and pathogenic yeast, as well as methods of using mitochondrial inhibitors to provide anti-aging benefits. Specific mitoriboscin compounds and groups of mitoriboscins are also disclosed.

The present disclosure relates to inhibitors of mitochondrial function. Methods of screening compounds for mitochondrial inhibition are disclosed. Also described are methods of using mitochondrial inhibitors called mitoriboscins—mitochondrial-based therapeutic compounds having anti-cancer and antibiotic properties—to prevent or treat cancer, bacterial infections, and pathogenic yeast, as well as methods of using mitochondrial inhibitors to provide anti-aging benefits. Specific mitoriboscin compounds and groups of mitoriboscins are also disclosed.

The invention relates to substituted bicyclic compounds, which are useful for inhibition of BET protein function by binding to bromodomains, pharmaceutical compositions comprising these compounds, and use of the compounds and compositions in therapy.

Disclosed herein is a solid lyophilized vaginal dosage form that can have an effective amount of at least one active ingredient, a crystalline structure forming agent in an amount of about 5 wt. % to about 40 wt. %, based on the total weight of the lyophilized dosage form, and at least one polymeric mucoadhesive matrix forming agent. The dosage form can have a pH of about 4.0 to 5.0, and can disintegrate within 120 seconds after being contacted with a vaginal mucosa. A method of delivering an active ingredient to the vaginal mucosa using the disclosed solid dosage form is also described.

The present invention relates to non-hormonal compositions and methods for inducing a condition of aspermia, azoospermia, or severe oligozoospermia in the male subject such that these compositions and methods for administering the same may be used as male contraception. Embodiments of the present invention may comprise a composition comprising an alpha-1-adrenoreceptor antagonist, such as (R)-silodosin, for daily administration to a male subject. The compositions and related methods may further include pharmaceutically acceptable carriers. The present invention further includes formulations which allow for a delay such that delayed or missed dose(s) do not nullify the contraceptive effect of the treatment regimen. Such compositions and methods may also avoid the side effects associated with typical formulations of alpha-1-adrenoreceptor antagonists.