A triptolide derivative, a preparation method therefor, and a method for use thereof are described. The triptolide derivative has the structure as shown in general formula I, and the definition of each substituent is as described in the description and claims. The triptolide derivative has improved immunosuppressive activity and anti-tumor activity, low toxicity and high safety, thus having good development and application prospects. ##STR00001##

The invention relates to the field of medicine and to the chemical and pharmacological industry, and concerns medicaments for the treatment of breast cancer. In particular the invention relates to a use of 3-O-sulfamoyloxy-7β-methyl-D-homo-6-oxa-8α-estra-1,3,5(10)-trien-17a-one as an anti-cancer agent in monotherapy and adjuvant therapy of breast cancer, including the triple negative breast cancer, and a method for the production of the said agent.

A triptolide derivative, a preparation method therefor, and a method for use thereof are described. The triptolide derivative has the structure as shown in general formula I, and the definition of each substituent is as described in the description and claims. The triptolide derivative has improved immunosuppressive activity and anti-tumor activity, low toxicity and high safety, thus having good development and application prospects.

##STR00001##

Biotransformation of an aromatase inhibitor, testolactone (1), yielded five new metabolites, 7α-hydroxy-3-oxo-13,17-secoandrosta-1,4-dieno-17,13α-lactone (2), 7β-hydroxy-3-oxo-13,17-seco-5β-androsta-1-eno-17,13α-lactone (3), 3α,11β-dihydroxy-13,17-seco-5β-androsta-17,13α-lactone (4), 4β,5β-epoxy-3β-hydroxy-13,17-secoandrosta-1-eno-17,13α-lactone (5), and 4β,5β-epoxy-3α-hydroxy-13,17-secoandrosta-1-eno-17,13α-lactone (6). 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 and several other diseases caused by overexpression of aromatase enzyme. Metabolites 3 (IC.sub.50=8.60±0.402 nM), and 4 (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 μM), and the standard aromatase inhibiting drug, exemestane (IC.sub.50=0.232±0.031 μM). Derivatives 2 (IC.sub.50=11.68±0.73 μM), 5 (IC.sub.50=10.37±0.50 μM) and 6 (IC.sub.50=0.82±0.059 μM) have also a good inhibition against aromatase enzyme. Therefore, metabolites 2-6 have the potential to serve as therapeutic agents against diseases caused by aromatase enzyme, including breast cancer.

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.

Disclosed herein are novel sialyltransferase inhibitors, and compositions and methods for treating diseases and/or conditions associated with the activation of sialyltransferase, such as a cancer, an immune disease or an inflammatory disease.

Provided herein is a compound of Formula (I-I), or a pharmaceutically acceptable salt thereof, wherein the variables are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I-I), and methods of using the compounds, e.g. in the treatment of CNS-related disorders.

##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 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.

The present invention addresses the problem of providing a novel chemically activated water-soluble prodrug. The present invention provides a compound represented by formula (1), or a pharmacologically acceptable salt thereof (in the formula, A represents A-0; X.sup.1 and X.sup.2 are the same as or different from each other and each independently represent a hydroxyl group or OC(O)Y(C(R.sup.1A) (R.sup.1B))n-NHR.sup.2, where X.sup.1 and X.sup.2 are not simultaneously hydroxyl groups, n is 2, 3, or 4, Y represents an oxygen atom or NR.sup.4, R.sup.1A and R.sup.1B are the same as or different from each other and each independently represent a hydrogen atom, etc., and R.sup.2 represents a hydrogen atom, etc.; and R.sup.a to R.sup.d are optionally present, are the same as or different from each other, and each independently represent a hydrogen atom, etc.).