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.

Provided herein is a compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein R.sup.19, R.sup.5, R.sup.3a, R.sup.1a, R.sup.1b, R.sup.2a, R.sup.2b, 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.12a, R.sup.12b, R.sup.18, R.sup.D, and q are defined herein. L is selected from the group consisting of: wherein A indicates the point of attachment at C17 and wherein X is selected from the group consisting of —C(0)N(R.sup.55a)(R.sup.55b), —N(R.sup.55a)(R.sup.55b), —N(R.sup.55b)C(O)(R.sup.55a), and R.sup.55C wherein R.sup.55c is carbon-bound substituted or unsubstituted heteroaryl or substituted or unsubstituted aryl. 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.

##STR00001##

Provided herein is a compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein R.sup.19, R.sup.5, R.sup.3a, R.sup.1a, R.sup.1b, R.sup.2a, R.sup.2b, 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.12a, R.sup.12b, R.sup.18, R.sup.D, and q are defined herein. L is selected from the group consisting of: wherein A indicates the point of attachment at C17 and wherein X is selected from the group consisting of —C(O)N(R.sup.55a)(R.sup.55b) N(R.sup.55a)(R.sup.55b), —N(R.sup.55b)C(O)(R.sup.55a), and R.sup.55C wherein R.sup.55c is carbon-bound substituted or unsubstituted heteroaryl or substituted or unsubstituted aryl. 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.

##STR00001##

Provided herein is a compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein R.sup.19, R.sup.5, R.sup.3a, R.sup.1a, R.sup.1b, R.sup.2a, R.sup.2b, 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.12a, R.sup.12b, R.sup.18, R.sup.D, and q are defined herein. L is selected from the group consisting of: wherein A indicates the point of attachment at C17 and wherein X is selected from the group consisting of —C(O)N(R.sup.55a)(R.sup.55b), —N(R.sup.55a)(R.sup.55b), —N(R.sup.55b)C(O)(R.sup.55a), and R.sup.55C wherein R.sup.55c is carbon-bound substituted or unsubstituted heteroaryl or substituted or unsubstituted aryl. 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.

##STR00001##

Chemical entities that are bufalin derivatives, pharmaceutical compositions and methods of treatment of cancer are described.

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.

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.

What is described is a compound of formula (1) ##STR00001##
wherein R.sub.1 and R.sub.2 are the same or different, each a linear or branched alkyl with 1-9 carbons, or an alkenyl or alkynyl with 2 to 11 carbon atoms; L.sub.1 and L.sub.2 are the same or different, each a linear alkyl having 5 to 18 carbon atoms, or form a heterocycle with N; X.sub.1 is a bond, or is —CO—O— whereby L.sub.2-CO—O—R.sub.2 is formed; X.sub.2 is S or O; L.sub.3 is a bond or a lower alkyl, or form a heterocycle with N; R.sub.3 is a lower alkyl; and R.sub.4 and R.sub.5 are the same or different, each a lower alkyl;
or a pharmaceutically acceptable salt thereof.

A highly effective synthetic route to produce donor-acceptor azetines through the highly enantioselective [3+1]-cycloaddition of silyl-protected enoldiazoacetates with aza-ylides using chiral copper(I) catalysis is provided. In one embodiment, the 2-azetidine cycloaddition products undergo generation of 3-azetidinones by reactions with nucleophiles that produce a broad spectrum of peptide products by the retro-Claisen reaction provided by facile strain with high efficacy and complete retention of enantiopurity. This ring opening reaction uncovers a new methodology for the attachment of chiral peptide units to a variety of amines and alcohols, and tolerates a broad scope of nucleophiles including naturally occurring amines, alcohols, amino acids, and other nitrogen based nucleophiles.

The present disclosure describes compositions, preparations, nanoparticles (such as lipid nanoparticles), and/or nanomaterials and methods of their use.