The present disclosure provides compounds that are cGAS antagonists, methods of preparation of the compounds, pharmaceutical compositions comprising the compounds, and their use in medical therapy.

The present disclosure provides compounds that are cGAS antagonists, methods of preparation of the compounds, pharmaceutical compositions comprising the compounds, and their use in medical therapy.

Disclosed herein are methods of increasing the sensitivity of cancer cells to cell death by an apoptosis-inducing drug. Also disclosed herein are methods of treating cancer in a subject and combination therapeutics.

Methods are provided for modulating MRGPR X2 generally, or for treating a MRGPR X2 or a MRGPR X2 ortholog dependent condition, more specifically, by contacting the MRGPR X2 or the MRGPR X2 ortholog by administering to a subject in need thereof, respectively, an effective amount of a compound having structure (I):

##STR00001##

or a pharmaceutically acceptable salt, isomer, hydrate, solvate or isotope thereof, wherein W, Z, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.x are as defined herein. Pharmaceutical compositions containing such compounds, as well as the compounds themselves, are also provided.

Methods are provided for modulating MRGPR X2 generally, or for treating a MRGPR X2 or a MRGPR X2 ortholog dependent condition, more specifically, by contacting the MRGPR X2 or the MRGPR X2 ortholog by administering to a subject in need thereof, respectively, an effective amount of a compound having structure (I):

##STR00001##

or a pharmaceutically acceptable salt, isomer, hydrate, solvate or isotope thereof, wherein W, Z, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.x are as defined herein. Pharmaceutical compositions containing such compounds, as well as the compounds themselves, are also provided.

A compound having anticancer activity, or a pharmaceutically acceptable salt thereof is provided. Used is a compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof: ##STR00001##
(wherein, L.sup.1 and L.sup.2 are the same or different and each represents a group represented by one formula selected from the group consisting of formulas (A) to (F), and S represents a group represented by one formula selected from the group consisting of formulas (S1) to (S18)).

A compound having anticancer activity, or a pharmaceutically acceptable salt thereof is provided. Used is a compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof: ##STR00001##
(wherein, L.sup.1 and L.sup.2 are the same or different and each represents a group represented by one formula selected from the group consisting of formulas (A) to (F), and S represents a group represented by one formula selected from the group consisting of formulas (S1) to (S18)).

A compound having anticancer activity, or a pharmaceutically acceptable salt thereof is provided. Used is a compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof:

##STR00001##

(wherein, L.sup.1 and L.sup.2 are the same or different and each represents a group represented by one formula selected from the group consisting of formulas (A) to (F), and S represents a group represented by one formula selected from the group consisting of formulas (S1) to (S18)).

A compound having anticancer activity, or a pharmaceutically acceptable salt thereof is provided. Used is a compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof:

##STR00001##

(wherein, L.sup.1 and L.sup.2 are the same or different and each represents a group represented by one formula selected from the group consisting of formulas (A) to (F), and S represents a group represented by one formula selected from the group consisting of formulas (S1) to (S18)).

Despite recent efforts to eradicate malaria worldwide, this parasitic disease is still considered a major public health problem, with a total of 219 million malaria cases and 435,000 deaths in 2017 After a decade of use, however, resistance to CQ has emerged in some locations, including Southeast Asia, South America, and the Western Pacific region, spreading progressively into malaria-endemic areas, including Africa, where increases in malaria mortality have been observed. This has led, in recent years, to the adoption of artemisinin-based combination therapies. Artemisinin-based combination therapies remain effective in most parts of the world, but recent cases of resistance in Southeast Asia call for new approaches and especially new drugs to treat malaria. Thus, the present invention features CQ analogues of Formula (I) that exhibited high activity against CQ-sensitive and CQ-resistant blood parasites and were also active in mice. The present invention also provides pharmaceutical compositions comprising the compounds of Formula (I), use of said compounds, and methods for treating conditions caused by blood parasites.