Compounds are provided according to Formula (I) and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.8 are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.

##STR00001##

A transfection reagent composition comprising: 30-60 MOL. % of a cationic lipid, or a pharmaceutical acceptable salt thereof; 10-60 MOL % of a structural lipid; 10-20 MOL % of a triglyceride; and 0.1 to about 10 MOL. % of a stabilizing agent, is provided. The transfection agent is effective in transfecting cells, particularly neurons, with siRNA, mRNA and plasmid nucleic acid, Sand maintaining viability of the cells as well as activity of the delivered nucleic acid.

The present invention relates to compounds which are intermediates in the synthesis of bile acid derivatives with pharmacological activity. The invention relates to compounds of general formula (I): ##STR00001##
wherein: , R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and Y are as defined herein. The compounds are intermediates in the synthesis of synthetic bile acids which are useful in the treatment of conditions such as liver disease. In addition, the invention relates to a method of synthesizing these intermediates and a method of preparing obeticholic acid and obeticholic acid analogues from the compounds of the invention.

GCPII inhibitors comprising 2-(phosphonomethyl) pentanedioic acid (2-PMPA) conjugated to a bile acid and their use for treating a disease or condition associated with elevated levels of GCPII, including inflammatory bowel disease.

The present invention includes DNP derivatives that are useful for preventing or treating a metabolic disease or disorder in a subject in need thereof. In certain embodiments, the subject is further administered at least one additional therapeutic agent.

Provided herein is a compound of Formula (I): ##STR00001##
or a pharmaceutically acceptable salt thereof, wherein R.sup.1a, R.sup.1b, R.sup.2a, R.sup.2b, R.sup.3, R.sup.4a, R.sup.4b, R.sup.5, R.sup.6a, R.sup.6b, R.sup.7a, R.sup.7a, R.sup.11a, R.sup.11b, R.sup.12a, R.sup.12b, R.sup.16a, R.sup.16b, R.sup.19, R.sup.11a, R.sup.22, R.sup.X, R.sup.Y and n are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) and methods of using the compounds, e.g., in the treatment of CNS-related disorders.

This application is directed to the use of aminosteroid compounds for the selective inhibition of the enzyme PTP1B in a mammal for the treatment of diabetes.

Compounds are provided according to Formula (I) and pharmaceutically acceptable salts thereof, wherein Z is a group of the formula (i), (ii), (iii), (iv), or (v), and wherein L.sup.1, L.sup.2, L.sup.3, X.sup.1, X.sup.2, Y, R.sup.z4, R.sup.z5, R.sup.z6, n, R.sup.1, R.sup.2, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b, R.sup.6a, R.sup.6b, R.sup.7a, R.sup.7b, R.sup.11a, R.sup.11b, R.sup.14, R.sup.17, R.sup.19, R.sup.20, R.sup.23a, R.sup.23b, and R.sup.24 are as defined herein, and pharmaceutical compositions thereof. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of CNS-related conditions in mammals.

##STR00001##

The application relates to compounds of formula A:

##STR00001##

or a salt, solvate, ester, tautomer, amino acide conjugate, or metabolite thereof. The compounds of formula A are TGR5 modulators useful for the treatment of various diseases, including metabolic disease, inflammatory disease, autoimmune disease, cardiac disease, kidney disease, cancer, and gastrointestinal disease.

Described herein are neuroactive steroids of the Formula (II): or a pharmaceutically acceptable salt thereof; wherein A, R.sup.1, R.sup.2a, R.sup.2b, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b, R.sup.5, R.sup.6 and are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use and treatment, e.g., such for inducing sedation and/or anesthesia.

##STR00001##