The present disclosure generally relates to compounds of Formula (1) and pharmaceutical compositions that may be used in methods of treating cancer. ##STR00001##

Provided herein, inter alia, is the synthesis of ETP derivatives. The uses of the ETP derivatives described herein include treatment of cancer.

Provided herein, inter alia, is the synthesis of ETP derivatives. The uses of the ETP derivatives described herein include treatment of cancer.

The present invention relates to novel substituted bridged urea compounds, corresponding related analogs, pharmaceutical compositions and methods of use thereof. Sirtuin-modulating compounds of the present invention may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. The present invention also related to compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

The present invention relates to novel substituted bridged urea compounds, corresponding related analogs, pharmaceutical compositions and methods of use thereof. Sirtuin-modulating compounds of the present invention may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. The present invention also related to compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

The present invention relates to novel substituted bridged urea compounds of Formula (I): ##STR00001##
or a pharmaceutically acceptable salt thereof, corresponding related analogs, pharmaceutical compositions and methods of use thereof. Sirtuin-modulating compounds of the present invention may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. The present invention also related to compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

The present invention relates to novel substituted bridged urea compounds of Formula (I): ##STR00001##
or a pharmaceutically acceptable salt thereof, corresponding related analogs, pharmaceutical compositions and methods of use thereof. Sirtuin-modulating compounds of the present invention may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. The present invention also related to compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

Disclosed are various synthetic methods to prepare structural analogs of largazole and derivatives thereof. One structural analog is an amide isostere of largazole. Another structural analog replaces the thiazole ring of largazole with a pyridine moiety or an oxazole moiety. Also disclosed are various intermediate compounds obtained when preparing structural analogs of largazole and derivatives thereof, including macrocycle analogs having an alcohol functionality.

Disclosed are various synthetic methods to prepare structural analogs of largazole and derivatives thereof. One structural analog is an amide isostere of largazole. Another structural analog replaces the thiazole ring of largazole with a pyridine moiety or an oxazole moiety. Also disclosed are various intermediate compounds obtained when preparing structural analogs of largazole and derivatives thereof, including macrocycle analogs having an alcohol functionality.

Provided are compounds of Formula (I), or pharmaceutically acceptable salts thereof, wherein i.a. Ring A is phenylene or 5- to 6-membered heteroarylene; Ring B is phenylene, 5- to 6-membered heterocycloalkylene or 5- to 6-membered heteroarylen; R.sup.4 is absent, heteroarylene, arylene, C1-3 alkylene, or R.sup.4 and R.sup.3 taken together with the nitrogen to which they are bound form a 3- to 7-membered heterocycloalkyl ring; R.sup.5 is absent, C(O)NR.sup.51, NR.sup.52 or O; R.sup.6 is C2-10 alkylene or alkenylene, wherein one or two of the carbon atoms in the alkylene chain is optionally replaced by an O, S, SO, SO.sub.2 or NR.sup.61, and wherein two of the carbon atoms in the alkylene chain are optionally connected by a two or three carbon atom alkylene chain to form a 5- to 7-membered ring; R.sup.7 is absent, NR.sup.71 or O. The compounds are IRAK4 inhibitors useful for the treatment of inflammatory diseases. ##STR00001##