Various prodrug compounds having the general structure: Active agent-(acid)-(linker)-SO.sub.2NR.sub.1R.sub.2 are described herein. Compounds having this general structure were shown to be more orally active than the unmodified parent molecule.

Novel methods for prevention, reduction or elimination of the incidence of male androgen deficiency symptoms or diseases including male hypogonadism-associated symptoms and diseases associated with low serum testosterone and/or low DHEA or low total androgens in susceptible warm-blooded animals including humans involving administration of an amount of a sex steroid precursor, particularly dehydroepiandrosterone (DHEA) and a selective estrogen receptor modulator (SERM) (particularly acolbifene), an antiestrogen or a prodrug of the two. The symptoms or diseases are loss of libido, erectile dysfunction, tiredness, loss of energy, depression, bone loss, muscle loss, muscle weakness, fat accumulation, memory loss, cognition loss, Alzheimer's disease, dementia, loss of body hair, fertility problems, insomnia, gynecomastia, anemia, hot flushes, sweats, decreased sense of well-being, obesity, osteoporosis, hypercholesterolemia, hyperlipidemia, atherosclerosis, hypertension, insulin resistance, cardiovascular disease and type 2 diabetes. Pharmaceutical compositions for delivery of active ingredient(s) and kit(s) useful to the invention are also disclosed.

A pharmaceutical formulation of testosterone undecanoate is provided. Methods of treating a testosterone deficiency or its symptoms with the inventive formulations are also provided.

Provided herein are steroid containing compositions suitable for providing therapeutically effective amounts of at least one steroid to individuals. Also provided herein are compositions comprising testosterone and/or testosterone derivatives suitable for providing therapeutically effective and safe amounts of testosterone over periods of time. Further provided are methods of treating andro- and/or testosterone deficiency in individuals by administering to the individuals compositions described herein.

This invention relates to proliposomal powder dispersions of testosterone undecanoate (TU) and phospholipids, including dispersions of TU and palmitoylphosphatidylcholine (DPPC), wherein the weight/weight (w/w) ratio of TU:DPPC in the proliposomal powder dispersion is about 1:2; or TU and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), wherein the weight/weight (w/w) ratio of TU:DMPC in the proliposomal powder dispersion is about 1:3; or TU and a 1-myristoyl-2-palmitoyl-sn-glycero 3-phosphocholine (MPPC), wherein the weight/weight (w/w) ratio of TU:MPPC in the proliposomal powder dispersion is about 1:3.

The present invention relates to solid forms of (S)—N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanophenoxy)-2-hydroxy-2-methylpropanamide and process for producing the same.

The present disclosure is directed to generally methods and/or compositions for treating mammographic breast density and/or breast stiffness in a patient in need thereof, such as a pre-menopausal, a peri-menopausal or a post-menopausal patient, comprising the administration of an effective amount of androgenic agent and an effective amount of an aromatase inhibitor. The present disclosure is also directed to methods and/or compositions for reducing breast pain. The present disclosure is also directed to method and/or compositions for reducing elasticity and/or decreasing mechano-transduction on the genome of breast cells. The present disclosure is also directed to methods and/or compositions for stabilizing and/or increasing the levels of androgen receptor expression in breast tissue.

The invention relates to a pharmaceutical composition in the form of a system in film form for transmucosal administration of steroid hormones. An administration system for steroid hormones which dissolves in the mouth and which releases with a high bioavailability is disclosed. The administration system in film form dissolves in the mouth preferably in a period of less than 30 min, and the steroid hormone entering the bloodstream transmucosally from the administration system leads to a rapid rise in the concentration in the blood. It is thus possible to achieve a maximum concentration of this steroid hormone in the blood in a period of less than 60 min after administration.

The present invention relates to a compound of Formula 1, 2 or 3: I II III wherein A is N or —CR.sub.0—, where R.sub.0 is hydrogen, C.sub.1-C.sub.6 linear or branched chain alkyl, etc., Z is —CR.sub.e—, or, —N—, where R.sub.e is hydrogen, C.sub.1-C.sub.6 linear or branched chain alkyl, etc.; R.sub.1 is hydrogen, C.sub.1-C.sub.6 linear or branched chain alkyl, etc.; R.sub.2 are independently hydrogen or C.sub.1-C.sub.6 linear or branched chain alkyl; R.sub.3 and R.sub.4 are independently hydrogen, C.sub.1C.sub.6 linear or branched chain alkyl, etc.; R.sub.5 and R.sub.6 are independently hydrogen or C.sub.1-C.sub.6 linear or branched chain alkyl, etc.; R.sub.8 is hydrogen, C.sub.1-C.sub.6 linear or branched chain alkyl, etc.; R.sub.9 and R.sub.10 are independently hydrogen or C.sub.1-C.sub.6 linear or branched chain alkyl, etc.; Q is —CO—, —(CH.sub.2).sub.q—, —(CHR.sub.s).sub.q—, or —(CR.sub.sR.sub.t).sub.q—, where R.sub.s and R.sub.t are independently C.sub.1-C.sub.6 linear or branched chain alkyl, aryl, alkylaryl, heteroaryl or alkylheteroaryl; where .sub.q is 0, 1, 2, or 3; and, where n is 0, 1, 2, 3, 4 or 5; or, a pharmaceutically acceptable salt thereof, for the treatment of certain diseases, particularly those affected or mediated by the androgen receptor; to combinations comprising such compounds with a second pharmaceutically active ingredient; to compositions containing such combinations; and to such combinations for the treatment of various diseases, particularly, those affected or mediated by the androgen receptor.

##STR00001##

The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of TYK2, and the treatment of TYK2-mediated disorders.