Described herein are compounds that are farnesoid X receptor agonists, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders associated with farnesoid X receptor activity.

The invention provides amides that inhibit cellular necrosis and/or human receptor interacting protein 1 kinase (RIP1), including corresponding sulfonamides, and pharmaceutically acceptable salts, hydrates and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof with an effective amount of the compound or composition, and detecting a resultant improvement in the person's health or condition.

The present invention relates to processes, process steps and intermediates useful in the asymmetric bisamidation of malonic ester derivatives wherein the new processes, process steps and intermediates are, for example, useful in the preparation of asymmetric malonic acid bisanilides such as cabozantinib.

The present invention relates to processes, process steps and intermediates useful in the asymmetric bisamidation of malonic ester derivatives wherein the new processes, process steps and intermediates are, for example, useful in the preparation of asymmetric malonic acid bisanilides such as cabozantinib.

Disclosed are a series of malonamide derivatives having a chemical structure(I), their synthesis, and evaluation of their bioactivities against bacterial cell, bacterial-infected C.elegans and mice.

Disclosed are a series of malonamide derivatives having a chemical structure(I), their synthesis, and evaluation of their bioactivities against bacterial cell, bacterial-infected C.elegans and mice.

A process for preparing a compound of Formula I is disclosed, comprising the steps:

##STR00001##

wherein: R.sup.1 is halo; R.sup.2 is halo; R.sup.3 is (C.sub.1-C.sub.6)alkyl or (C.sub.1-C.sub.6)alkyl optionally substituted with heterocycloalkyl; R.sup.4 is (C.sub.1-C.sub.6)alkyl; and Q is CH or N;
comprising: (a) contacting 1,1-cyclopropane dicarboxylic acid with thionyl chloride in a polar aprotic solvent;

##STR00002## (b) adding and a tertiary amine base to the mixture of step (a) to form a compound of Formula A; and

##STR00003## (c) coupling a compound of Formula A with an amine of Formula B to form a compound of Formula I.

##STR00004##

A process for preparing a compound of Formula I is disclosed, comprising the steps:

##STR00001##

wherein: R.sup.1 is halo; R.sup.2 is halo; R.sup.3 is (C.sub.1-C.sub.6)alkyl or (C.sub.1-C.sub.6)alkyl optionally substituted with heterocycloalkyl; R.sup.4 is (C.sub.1-C.sub.6)alkyl; and Q is CH or N;
comprising: (a) contacting 1,1-cyclopropane dicarboxylic acid with thionyl chloride in a polar aprotic solvent;

##STR00002## (b) adding and a tertiary amine base to the mixture of step (a) to form a compound of Formula A; and

##STR00003## (c) coupling a compound of Formula A with an amine of Formula B to form a compound of Formula I.

##STR00004##

A process for preparing a compound of Formula I is disclosed, comprising the steps:

##STR00001##

wherein: R.sup.1 is halo; R.sup.2 is halo; R.sup.3 is (C.sub.1-C.sub.6)alkyl or (C.sub.1-C.sub.6)alkyl optionally substituted with heterocycloalkyl; R.sup.4 is (C.sub.1-C.sub.6)alkyl; and Q is CH or N;
comprising: (a) contacting 1,1-cyclopropane dicarboxylic acid with thionyl chloride in a polar aprotic solvent;

##STR00002## (b) adding and a tertiary amine base to the mixture of step (a) to form a compound of Formula A; and

##STR00003## (c) coupling a compound of Formula A with an amine of Formula B to form a compound of Formula I.

##STR00004##

The present invention relates to a process for preparing Lomitapide or its pharmaceutically acceptable salt thereof having high purity with acceptable levels of impurities.