Provided herein are small molecule active metabotropic glutamate subtype-2 and -3 receptor negative allosteric modulators (NAMs), compositions comprising the compounds, and methods of using the compounds and compositions.

Disclosed are compounds of formula (I) or a pharmaceutically acceptable salt thereof, pharmaceutical compositions containing them, and to a process for the preparation of the compounds: ##STR00001##
R.sup.1 is independently selected from hydrogen atom, amine group, monocyclic or bicyclic aliphatic, aromatic, heteroaliphatic or heteroaromatic ring. R.sup.2 is independently selected from monocyclic or bicylic aliphatic, heteroaliphatic, aromatic or heteroaromatic ring, C.sub.1-C.sub.6 alkyl, alkenyl or alkynyl chain. n is 1 or 2; preferably n is 1. m is 0, 1 or 2; preferably m is 0. R.sup.3 and R.sup.4 can be, independently, —H, —F, C.sub.1-C.sub.4 alkyl, —OH, —OC.sub.1-C.sub.4 alkyl; preferably they are both —H. X is O or S. R.sup.5 is —H or —CH.sub.3 optionally substituted by one or more fluorine atoms; preferably R.sup.5 is hydrogen. The compounds can be used in the treatment of conditions or diseases mediated by P2X7 receptor.

Disclosed are compounds of formula (I) or a pharmaceutically acceptable salt thereof, pharmaceutical compositions containing them, and to a process for the preparation of the compounds: ##STR00001##
R.sup.1 is independently selected from hydrogen atom, amine group, monocyclic or bicyclic aliphatic, aromatic, heteroaliphatic or heteroaromatic ring. R.sup.2 is independently selected from monocyclic or bicylic aliphatic, heteroaliphatic, aromatic or heteroaromatic ring, C.sub.1-C.sub.6 alkyl, alkenyl or alkynyl chain. n is 1 or 2; preferably n is 1. m is 0, 1 or 2; preferably m is 0. R.sup.3 and R.sup.4 can be, independently, —H, —F, C.sub.1-C.sub.4 alkyl, —OH, —OC.sub.1-C.sub.4 alkyl; preferably they are both —H. X is O or S. R.sup.5 is —H or —CH.sub.3 optionally substituted by one or more fluorine atoms; preferably R.sup.5 is hydrogen. The compounds can be used in the treatment of conditions or diseases mediated by P2X7 receptor.

Disclosed herein are FABP4 and FABP5 inhibitor compounds and their use in pharmaceutical compositions for treating diseases relating to fatty acid metabolism, including cancer. Also disclosed herein are methods for preparing the disclosed compounds.

Disclosed herein are FABP4 and FABP5 inhibitor compounds and their use in pharmaceutical compositions for treating diseases relating to fatty acid metabolism, including cancer. Also disclosed herein are methods for preparing the disclosed compounds.

The present application describes a substituted aryl compound used as an RAD51 inhibitor and a pharmaceutically acceptable salt thereof. The compound has the structure as represented by Formula (I) and has the substituents and structural features as described in the present application. Furthermore, the present application describes a pharmaceutical composition containing the compound as represented by Formula (I) or the pharmaceutically acceptable salt thereof, and the use of the compound as represented by Formula (I) or the pharmaceutically acceptable salt thereof and the pharmaceutical composition containing same in the preparation of a drug for preventing or treating RAD51 mediated diseases.

##STR00001##

The present application describes a substituted aryl compound used as an RAD51 inhibitor and a pharmaceutically acceptable salt thereof. The compound has the structure as represented by Formula (I) and has the substituents and structural features as described in the present application. Furthermore, the present application describes a pharmaceutical composition containing the compound as represented by Formula (I) or the pharmaceutically acceptable salt thereof, and the use of the compound as represented by Formula (I) or the pharmaceutically acceptable salt thereof and the pharmaceutical composition containing same in the preparation of a drug for preventing or treating RAD51 mediated diseases.

##STR00001##

Methods are provided for modulating MRGPR X4 generally, or for treating a MRGPR X4 dependent condition more specifically, by contacting the MRGPR X4 or administering to a subject in need thereof, respectively, an effective amount of a compound having the structure of Formula (I): ##STR00001##
or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof, wherein n, x, A, Q.sub.1, Q.sub.2, Z, R, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as defined herein. Pharmaceutical compositions containing such compounds, as well as to compounds themselves, are also provided.

Thiadiazolyl-oximinoacetic acid derivatives have been synthesized, which are useful in the manufacture of cephalosporin antibiotic compounds. Compound (1) (TATD) is commercially available (CAS No. 76028-96-1). It has now been discovered that the thiadiazolyl-oximinoacetic acid derivative compound (1) (TATD) can be prepared from dimethyl malonate (SM 1, CAS No. 108-59-8) according to methods described herein. The methods provide products having desirable purity.

Thiadiazolyl-oximinoacetic acid derivatives have been synthesized, which are useful in the manufacture of cephalosporin antibiotic compounds. Compound (1) (TATD) is commercially available (CAS No. 76028-96-1). It has now been discovered that the thiadiazolyl-oximinoacetic acid derivative compound (1) (TATD) can be prepared from dimethyl malonate (SM 1, CAS No. 108-59-8) according to methods described herein. The methods provide products having desirable purity.