2-hydroxy-benzoic anilide compounds and derivatives, compositions thereof, and methods for treating metabolic diseases and cancer through uncoupling mitochondria.

The present disclosure provides a process for the preparation of 2-(2-amino propan-2-yl)-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydro-pyrimidine-4-carboxamide by debenzylation of benzyl(2-{4-[(4-fluorobenzyl)carbamoyl]-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl}propan-2-yl)carbamate. This process may be used in the synthesis of raltegravir and pharmaceutically acceptable salts thereof.

The present disclosure provides a process for the preparation of 2-(2-amino propan-2-yl)-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydro-pyrimidine-4-carboxamide by debenzylation of benzyl(2-{4-[(4-fluorobenzyl)carbamoyl]-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl}propan-2-yl)carbamate. This process may be used in the synthesis of raltegravir and pharmaceutically acceptable salts thereof.

Disclosed herein is a compound of formula (I), or a pharmaceutically acceptable salt thereof: (Formula (I)). Also disclosed herein are uses of a compound disclosed herein in the potential treatment or prevention of an IDO-associated disease or disorder. Also disclosed herein are compositions comprising a compound disclosed herein. Further disclosed herein are uses of a composition in the potential treatment or prevention of an IDO-associated disease or disorder. ##STR00001##

The invention provides certain nicotine salt co-crystals and provides novel polymorphic forms of certain nicotine salts. In particular, certain nicotine salt-co-crystals are described, including nicotine and two different coformers. The invention further provides methods of preparation and characterization of nicotine salts, co-crystals, and salt co-crystals. In addition, tobacco products, including smoking articles, smokeless tobacco products, and electronic smoking articles comprising nicotine salts, co-crystals, and/or salt co-crystals are also provided.

The invention provides certain nicotine salt co-crystals and provides novel polymorphic forms of certain nicotine salts. In particular, certain nicotine salt-co-crystals are described, including nicotine and two different coformers. The invention further provides methods of preparation and characterization of nicotine salts, co-crystals, and salt co-crystals. In addition, tobacco products, including smoking articles, smokeless tobacco products, and electronic smoking articles comprising nicotine salts, co-crystals, and/or salt co-crystals are also provided.

Provided is a method for producing an orotic acid derivative, the method comprising a condensation step of performing, under a basic condition, a condensation reaction between an orotic acid halide represented by General Formula (I) and a compound represented by General Formula (II) to generate an orotic acid derivative represented by General Formula (III); and a neutralization crystallization step of precipitating crystals of orotic acid by neutralization crystallization to separate a liquid containing the orotic acid derivative from the crystals of orotic acid, after the condensation step. In General Formula (I), (II), or (III), X is a halogen atom, and A is a group represented by General Formula (A-1) or (A-2). In General Formula (A-1) or (A-2), R.sup.1 is a hydrogen atom or an organic group, and R.sup.2 and R.sup.3 are each independently an organic group. In a case where R.sup.1 is an organic group, R.sup.1 and R.sup.2 may be bonded to each other to form a ring.

##STR00001##

Provided is a method for producing an orotic acid derivative, the method comprising a condensation step of performing, under a basic condition, a condensation reaction between an orotic acid halide represented by General Formula (I) and a compound represented by General Formula (II) to generate an orotic acid derivative represented by General Formula (III); and a neutralization crystallization step of precipitating crystals of orotic acid by neutralization crystallization to separate a liquid containing the orotic acid derivative from the crystals of orotic acid, after the condensation step. In General Formula (I), (II), or (III), X is a halogen atom, and A is a group represented by General Formula (A-1) or (A-2). In General Formula (A-1) or (A-2), R.sup.1 is a hydrogen atom or an organic group, and R.sup.2 and R.sup.3 are each independently an organic group. In a case where R.sup.1 is an organic group, R.sup.1 and R.sup.2 may be bonded to each other to form a ring.

##STR00001##

Nicotine materials, compositions including one or more nicotine material(s), and articles of manufacture comprising the nicotine material(s) and/or the composition(s), and uses of the nicotine materials, compositions, and articles of manufacture. The nicotine materials may be nicotine co-crystals, which may include one or more coformer(s), nicotine salts, or the like. The nicotine materials may be made by evaporation of one or more coformer(s), which independently may be solvent(s), and/or solvent(s), if present, from a nicotine material-forming solution. A nicotine material and/or a composition may be used in a nicotine delivery method.

The invention provides certain nicotine salt co-crystals and provides novel polymorphic forms of certain nicotine salts. In particular, certain nicotine salt-co-crystals are described, including nicotine and two different coformers. The invention further provides methods of preparation and characterization of nicotine salts, co-crystals, and salt co-crystals. In addition, tobacco products, including smoking articles, smokeless tobacco products, and electronic smoking articles comprising nicotine salts, co-crystals, and/or salt co-crystals are also provided.