The present invention relates generally to compositions and methods for treating cancer and hypercortisolism. Provided herein are substituted steroidal derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of glucocorticoid receptors. Furthermore, the subject compounds and compositions are useful for the treatment of cancer.

The present invention provides compounds of Formula I,

##STR00001##

pharmaceutical compositions comprising these compounds and methods of using these compounds to prevent or treat FXR-mediated or TGR5-mediated diseases or conditions.

Disclosed are compounds that accumulate in Gram-negative bacteria. Also disclosed are method of antimicrobial treatment using the compounds.

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.

The present invention relates to compounds of Formula (I), ##STR00001##
and pharmaceutically acceptable salts thereof, where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8 and m are as defined herein, pharmaceutical compositions comprising these compounds and methods of use of these compounds for treating a TGR5 mediated disease or condition.

Cationic steroidal antimicrobial (CSA) compounds having a structure of Formula I, II or III, or salt thereof, wherein at least one of at least one of R.sub.1-R.sub.18, (e.g., R.sub.3, R.sub.7 and R.sub.12) is linked to the steroidal backbone by a urethane group: ##STR00001##
At least one of R.sub.1-R.sub.18, (e.g., R.sub.3, R.sub.7 and R.sub.12) has the following urethanyl structure:
O(C?O)NR.sub.19R.sub.20
where R.sub.19 and R.sub.20 are independently hydrogen, alkyl, alkenyl, alkynyl, aryl, aminoalkyl, aminoalkenyl, aminoalkynyl, or aminoaryl, provided that at least one of R.sub.19 or R.sub.20 includes an amino group (e.g., R.sub.19 is hydrogen and R.sub.20 is (C.sub.2-C.sub.6)aminoalkyl). R.sub.18 can have the following structure:
R.sub.21(C?O)NR.sub.22R.sub.23
where R.sub.21 is omitted or alkyl, alkenyl, alkynyl, or aryl, and R.sub.22 and R.sub.23 are hydrogen, alkyl, alkenyl, alkynyl, or aryl, provided that at least one of R.sub.22 or R.sub.23 is not hydrogen.

The disclosure provides compounds, methods, and kits for diagnosis, detection, screening, and imaging of a disease condition (e.g., infection, cancer, tumor, neoplasia), in vitro, ex vivo, and/or in vivo. Certain embodiments include administering a cationic steroid antimicrobial (a CSA or ceragenin), the CSA including a steroidal backbone and a heterocyclic ring separated from the steroidal backbone by at least 4 atoms (and up to 24 atoms or more), to a subject having or at risk of having a disease condition in an amount effective to diagnose, detect, screen for or image the disease condition in the subject.

The present invention provides compounds of Formula I, ##STR00001##
pharmaceutical compositions comprising these compounds and methods of using these compounds to prevent or treat FXR-mediated or TGR5-mediated diseases or conditions.

The present disclosure relates generally to Cellular Signalling inhibitors of compound of Formula (I), compositions and formulations comprising the same, methods, processes, and uses thereof. In particular, the present disclosure provides CSF-1R inhibitors demonstrating sustained inhibition of CSF/CSF1R signalling pathway with decreased toxicity. The present disclosure also provides supramolecular combinatorial therapeutics, wherein a CSF-1R inhibitor is combined with one or more of a chemotherapeutic agent, a kinase inhibitor, and an immunoregulator, each of which is optionally conjugated with a lipid. The present disclosure also provides a method for treating cancer, allergy, Systemic lupus erythematosus, nephritis, Chronic Obstructive Pulmonary Disease, and abnormal macrophage functions or any combinations thereof.

##STR00001##

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.