Certain embodiments are directed to oridonin analogs or derivatives. In certain aspects, the derivatives are used as anticancer or anti-inflammatory agents.

Macrocyclic compounds having the structure of Formula (A), or pharmaceutically acceptable salts thereof, are provided,

##STR00001##

wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are defined herein. Also provided are pharmaceutical compositions comprising the macrocyclic compound and methods for treating cancer in a patient comprising administering to the patient the macrocyclic compound.

Macrocyclic compounds having the structure of Formula (A), or pharmaceutically acceptable salts thereof, are provided,

##STR00001##

wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are defined herein. Also provided are pharmaceutical compositions comprising the macrocyclic compound and methods for treating cancer in a patient comprising administering to the patient the macrocyclic compound.

Macrocyclic compounds having the structure of Formula (A), or pharmaceutically acceptable salts thereof, are provided, ##STR00001##
wherein R.sup.1, R.sup.2, Z.sup.1, Z.sup.2, v, T, L, R.sup.3, R.sup.4 and R.sup.5 are defined herein. Also provided are pharmaceutical compositions comprising the macrocyclic compound and methods for treating cancer in a patient comprising administering to the patient the macrocyclic compound.

Macrocyclic compounds having the structure of Formula (A), or pharmaceutically acceptable salts thereof, are provided, ##STR00001##
wherein R.sup.1, R.sup.2, Z.sup.1, Z.sup.2, v, T, L, R.sup.3, R.sup.4 and R.sup.5 are defined herein. Also provided are pharmaceutical compositions comprising the macrocyclic compound and methods for treating cancer in a patient comprising administering to the patient the macrocyclic compound.

The disclosure provides compounds of Formula (I), or a pharmaceutically acceptable salt thereof, wherein R-R.sup.7 and L are defined herein: Also provided are pharmaceutical compositions, comprising one or more compounds described herein and methods of treating cancer in a patient comprising administering to the patient a compound or pharmaceutical composition described herein.

##STR00001##

The disclosure provides compounds of Formula (I), or a pharmaceutically acceptable salt thereof, wherein R-R.sup.7 and L are defined herein: Also provided are pharmaceutical compositions, comprising one or more compounds described herein and methods of treating cancer in a patient comprising administering to the patient a compound or pharmaceutical composition described herein.

##STR00001##

Compound (I), deuterated derivatives, and pharmaceutically acceptable salts of any of the foregoing are disclosed. Methods of treating cystic fibrosis using these compounds are also disclosed. ##STR00001##

Compound (I), deuterated derivatives, and pharmaceutically acceptable salts of any of the foregoing are disclosed. Methods of treating cystic fibrosis using these compounds are also disclosed. ##STR00001##

This disclosure provides modulators of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), pharmaceutical compositions containing at least one such modulator, methods of treatment of CFTR mediated diseases, including cystic fibrosis, using such modulators and pharmaceutical compositions, combination pharmaceutical compositions and combination therapies employing those modulators, and processes and intermediates for making such modulators.