Provided are compounds generated by conjugation of triptolide with glucose to form glucose-triptolide conjugates, provides compounds with effective anti-proliferative activity and improved tolerability as compared to naturally occurring triptolide compounds.

Disclosed herein are methods of using immunomodulatory sterols as vaccine adjuvants. Accordingly, certain embodiments relates to pharmaceutical compositions containing at least one antigen and at least one immunomodulatory sterol; and, methods of inducing an immunomodulatory response in a patient by administering an immunomodulatory-effective amount of at least one immunomodulatory sterol.

The present disclosure provides for a synthetic strategy to incorporate a C12-hydroxy group from the methylene (CH2-) in a steroid backbone, combining synthetic chemistry and enzymology techniques to develop a selective inhibitor for cytochrome P450 8B1, and developing a selective P450 8B1 inhibitor, which can be used as a tool to study P450 8B1 and treat health issues.

The present invention refers to a new process for the synthesis of (9,10)-pregn-4-ene-3,20-dione, commonly known as retroprogesterone, having the formula (1) shown below. ##STR00001##

The invention provides a method for treating fibrosis, nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) in an animal, comprising administering to the animal, a compound of formula I:

##STR00001##

or a pharmaceutically acceptable salt thereof.

The present invention refers to a new process for the synthesis of (9,10)-pregn-4-ene-3,20-dione, commonly known as retroprogesterone, having the formula (1) shown below.

##STR00001##

Provided is a process for producing a compound, which has an oxo group specifically introduced on the 15-position of a steroid skeleton and which is useful as an intermediate, with a high yield without complicated steps. A compound represented by the formula (2) is allowed to react with an oxidant (e.g., a hypervalent iodine compound) and a co-oxidant (e.g., a peroxide) to produce a 15-oxosteroid compound represented by the formula (1), which is useful as an intermediate:

##STR00001##

wherein R.sub.1 to R.sub.3 are the same or different and each represent a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, or a haloalkoxy group, R.sub.4 represents a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, an acyl group, or an alkoxycarbonyl group, R.sub.5 represents a hydrogen atom, an alkyl group, or an acyl group, R.sub.6 represents a hydrogen atom, an alkyl group, an acyl group, or a sulfonyl group, X represents an oxygen atom (O) or a methylene group (CH.sub.2).

Provided is a crystalline polymorphic form A of 15-hydroxy-osaterone acetate having an improved stability (storage stability, pulverization stability, and absorption characteristics). In a powder X-ray diffraction spectrum, characteristic diffraction peaks of the crystalline polymorphic form A of 15-hydroxy-osaterone acetate appear at diffraction angles 2 of 9.60.2, 17.10.2, and 20.20.2. The crystalline polymorphic form A has a melting point of 280 to 283 C. and is a prism crystal.

Biotransformation of an aromatase inhibitor, testolactone (1), yielded four metabolites, 7?-hydroxy-3-oxo-13,17-seco-5?-androsta-1-eno-17,13?-lactone (2), 3?,11?-dihydroxy-13,17-seco-5?-androsta-17,13?-lactone (3), 4?,5?-epoxy-3?-hydroxy-13,17-secoandrosta-1-eno-17,13?-lactone (4), and 4?,5?-epoxy-3?-hydroxy-13,17-secoandrosta-1-eno-17,13?-lactone (5). Aromatase (estrogen synthase) involves in the synthesis of estrogen, and promotes the growth of breast cancerous cells. It is a key target for the discovery of chemotherapeutic agents against ER+(estrogen-positive) breast-cancers. Metabolites 2 (IC.sub.50=8.63?0.402 nM), and 3 (IC.sub.50=9.23?1.31 nM) were identified as potent inhibitors against human aromatase enzyme, in comparison to 1 (IC.sub.50=0.716?0.031 ?M), and the standard aromatase inhibiting drug, exemestane (IC.sub.50=0.232?0.031 ?M). Derivatives 4 (IC.sub.50=10.37?0.50 ?M) and 5 (IC.sub.50=0.82?0.059 ?M) also showed a good inhibition against aromatase enzyme. Therefore, metabolites 2-5 have the potential to serve as therapeutic agents against ER+ (estrogen-positive) breast-cancers.

The invention relates to new types of modulators of the cold menthol receptor TRPM8, to methods of modulating the TRPM8 receptor using these modulators; and in particular the use of the modulators for inducing a sensation of coldness; and also the articles and compositions produced using these modulators.