The present invention is related to an improved and efficient process for preparation of (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine which comprises: (a) N-acylation of 3-Amino-4-methyl pyridine; (b) Quarternization of 3-Acetylamino-4-methyl pyridine using benzyl halide; (c) Partial reduction of quarternized 3-Acetylamino-4-methyl pyridine by Sodium borohydride in Methanol or water; (d) Hydrolysis of partially reduced product to 1-Benzyl-4-methylpiperidin-3-one in presence of acid; (e) Reductive amination of 1-Benzyl-4-methylpiperidin-3-one using Methanolic methylamine in presence of Titanium(IV) isopropoxide in Methanol; (f) Resolution of 1-Benzyl-4-methylpiperidin-3-yl)-methylamine using Ditoluoyl (L) tartaric acid to get (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine. The invention is also related to novel intermediates: ##STR00001##
wherein R, R and X are as described in the specification.

Certain compounds, or pharmaceutically acceptable salts or prodrugs thereof, are provided herein. Also provided are pharmaceutical compositions comprising at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of KMO activity are described; which comprise administering to such patients an amount of at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include neurodegenerative disorders such as Huntington's disease. Also described are methods of treatment include administering at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein as a single active agent or administering at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein in combination with one or more other therapeutic agents. Also provided are methods for screening compounds capable of inhibiting KMO activity.

Certain compounds, or pharmaceutically acceptable salts or prodrugs thereof, are provided herein. Also provided are pharmaceutical compositions comprising at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of KMO activity are described; which comprise administering to such patients an amount of at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include neurodegenerative disorders such as Huntington's disease. Also described are methods of treatment include administering at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein as a single active agent or administering at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein in combination with one or more other therapeutic agents. Also provided are methods for screening compounds capable of inhibiting KMO activity.

There is provided a range of novel compounds which have been demonstrated to have useful UV absorbing properties. These compounds will find use in a range of applications such as active components in sunscreen formulations, paints, plastics, fabrics, glass and UV protective coatings.

There is provided a range of novel compounds which have been demonstrated to have useful UV absorbing properties. These compounds will find use in a range of applications such as active components in sunscreen formulations, paints, plastics, fabrics, glass and UV protective coatings.

The present disclosure is related to an improved and efficient process for preparation of (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine which comprises:

(a) N-acylation of 3-Amino-4-methyl pyridine; (b) Quarternization of 3-Acetylamino-4-methyl pyridine using benzyl halide; (c) Partial reduction of quarternized 3-Acetylamino-4-methyl pyridine by Sodium borohydride in Methanol or water; (d) Hydrolysis of partially reduced product to 1-Benzyl-4-methylpiperidin-3-one in presence of acid; (e) Reductive amination of 1-Benzyl-4-methylpiperidin-3-one using Methanolic methylamine in presence of Titanium(IV) isopropoxide in Methanol; (f) Resolution of 1-Benzyl-4-methylpiperidin-3-yl)-methylamine using Ditoluoyl (L) tartaric acid to get (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine. The disclosure is also related to novel intermediates:

##STR00001##

wherein R, R and X are as described in the specification.

Disclosed herein is a cost effective and environmentally friendly process to prepare 1-hydroxy-6-substituted pyridones from 2,6-dichloropyridine. The process includes the steps of (a) reacting 2,6-dichloropyridine with hydrogen peroxide in the presence of trifluoroacetic acid at a first temperature to produce a first intermediate containing (1) trifluoroacetic acid and (2) 2,6-dichloropyridine N-oxide and/or salts thereof; (b) adding sulfuric acid to the first intermediate to provide a second intermediate; (c) removing trifluoroacetic acid from the second intermediate to provide a composition containing 2,6-dichloropyridine N-oxide and/or salts thereof which is essentially free of trifluoroacetic acid; (d) reacting 2,6-dichloropyridine N-oxide and/or salts thereof from step (c) with RXH and a base wherein each R is independently a substituted or unsubstituted hydrocarbyl group having between 1 and 20 carbon atoms, X is oxygen or sulfur, to produce a corresponding 2,6-disubstituted-pyridine N-oxide; and (e) heating the disubstituted compound thereby producing the 1-hydroxy-6-substituted pyridone.

This invention is in the field of medicinal chemistry. In particular, the invention relates to mixed disulfide conjugates of thienopyridine compounds, and their use as therapeutics for the treatment, amelioration, and prevention of cardiovascular diseases.

This invention is in the field of medicinal chemistry. In particular, the invention relates to mixed disulfide conjugates of thienopyridine compounds, and their use as therapeutics for the treatment, amelioration, and prevention of cardiovascular diseases.

A NK.sub.1 antagonist having the formula (I),

##STR00001##

wherein Ar.sup.1 and Ar.sup.2 are optionally substituted phenyl or heteroaryl, X.sup.1 is an ether, thio or imino linkage, R.sup.4 and R.sup.5 are not both H or alkyl, and the remaining variables are as defined in the specification, useful for treating a number of disorders, including emesis, depression, anxiety and cough. Pharmaceutical compositions. Methods of treatment and combinations with other agents are also disclosed.