Phenyl or pyridinyl-ethynyl derivatives

A compound of formula IA,

• wherein
• Y is N or C—R3;
• R3 is hydrogen, methyl, halogen or nitrile;
• R1 is phenyl or pyridinyl, each of which is optionally substituted by halogen, lower alkyl or lower alkoxy;
• or a pharmaceutically acceptable acid addition salt, racemic mixture, corresponding enantiomer, optical isomer, or stereoisomer thereof.

A compound selected from the group consisting of

• 5-phenylethynyl-pyridine-2-carboxylic acid tert-butylamide;
• 5-phenylethynyl-pyridine-2-carboxylic acid tert-butyl-methyl-amide;
• 5-(3-fluoro-phenylethynyl)-pyridine-2-carboxylic acid tert-butyl-methyl-amide;
• 5-(4-fluoro-phenylethynyl)-pyridine-2-carboxylic acid tert-butyl-methyl-amide;
• 5-(2,5-difluoro-phenylethynyl)-pyridine-2-carboxylic acid tert-butyl-methyl-amide;
• 5-(4-fluoro-phenylethynyl)-pyrimidine-2-carboxylic acid tert-butylamide;
• 5-(3-fluoro-phenylethynyl)-pyrimidine-2-carboxylic acid tert-butylamide;
• 5-(4-fluoro-phenylethynyl)-pyrimidine-2-carboxylic acid tert-butyl-methyl-amide;
• 5-(3-fluoro-phenylethynyl)-pyrimidine-2-carboxylic acid tert-butyl-methyl-amide;
• and
• 5-m-tolylethynyl-pyrimidine-2-carboxylic acid tert-butylamide;
• or a pharmaceutically acceptable acid addition salt, racemic mixture, corresponding enantiomer, optical isomer, or stereoisomer thereof.

A compound selected from the group consisting of [5-(2,5-difluoro-phenylethynyl)-pyridin-2-yl]-(2,2-dimethyl-morpholin-4-yl)-methanone;

• [5-(3-fluoro-phenylethynyl)-pyridin-2-yl]-(4-hydroxy-4-methyl-piperidin-1-yl)-methanone;
• (RS)-(4-hydroxy-2,2-dimethyl-piperidin-1-yl)-(5-phenylethynyl-pyridin-2-yl)-methanone;
• (RS)-(4-hydroxy-3,3-dimethyl-piperidin-1-yl)-(5-phenylethynyl-pyridin-2-yl)-methanone;
• (RS)-[5-(4-fluoro-phenylethynyl)-pyridin-2-yl]-(4-hydroxy-3,3-dimethyl-piperidin-1-yl)-methanone;
• (RS)-[5-(3-fluoro-phenylethynyl)-pyridin-2-yl]-(4-hydroxy-3,3-dimethyl-piperidin-1-yl)-methanone;
• 3-chloro-5-phenylethynyl-pyridine-2-carboxylic acid tert-butyl-methyl-amide;
• and
• (3,3-difluoro-azetidin-1-yl)-(5-phenylethynyl-pyrimidin-2-yl)-methanone;
• or a pharmaceutically acceptable acid addition salt, racemic mixture, corresponding enantiomer, optical isomer, or stereoisomer thereof.

A compound selected from the group consisting of (3,3-dimethyl-piperidin-1-yl)-(5-phenylethynyl-pyrimidin-2-yl)-methanone;

• (RS)-(4-hydroxy-2,2-dimethyl-piperidin-1-yl)-(5-phenylethynyl-pyrimidin-2-yl)-methanone;
• (RS)-(4-hydroxy-3,3-dimethyl-piperidin-1-yl)-(5-phenylethynyl-pyrimidin-2-yl)-methanone;
• (RS)-[5-(3-fluoro-phenylethynyl)-pyrimidin-2-yl]-(4-hydroxy-3,3-dimethyl-piperidin-1-yl)-methanone;
• 3-fluoro-5-phenylethynyl-pyridine-2-carboxylic acid methyl-(3-methyl-oxetan-3-yl)-amide;
• (RS)-3-fluoro-5-phenylethynyl-pyridine-2-carboxylic acid methyl-(2,2,2-trifluoro-1-methyl-ethyl)-amide;
• 3-cyano-5-phenylethynyl-pyridine-2-carboxylic acid tert-butyl-methyl-amide;
• 5-(3-chloro-phenylethynyl)-pyridine-2-carboxylic acid methyl-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-amide;
• (RS)-5-(3-chloro-phenylethynyl)-pyridine-2-carboxylic acid (2,2,2-trifluoro-1-methyl-ethyl)-amide;
• and
• (RS)-5-(3-chloro-phenylethynyl)-pyridine-2-carboxylic acid methyl-(2,2,2-trifluoro-1-methyl-ethyl)-amide;
• or a pharmaceutically acceptable acid addition salt, racemic mixture, corresponding enantiomer, optical isomer, or stereoisomer thereof.

A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula I

• wherein
• Y is N or C—R3;
• R3 is hydrogen, methyl, halogen or nitrile;
• R1 is selected from the group consisting of pyridinyl, optionally substituted by halogen, lower alkyl or lower alkoxy, and phenyl substituted by halogen, lower alkyl or lower alkoxy;
• R2/R2′ are each independently hydrogen, lower alkyl or lower alkyl substituted by halogen,
• or R2 and R2′ together with the N-atom to which they are attached form a morpholine ring, a piperidine ring or an azetidine ring, each of which is unsubstituted or substituted one or more substituents selected from lower alkoxy, halogen, hydroxy and methyl;
• R4/R4′ are each independently hydrogen or lower alkyl,
• or R4 and R4′ together form tetrahydrofuran- or an oxetane-ring;
• or a pharmaceutically acceptable acid addition salt, racemic mixture, corresponding enantiomer, optical isomer, or stereoisomer thereof and a pharmaceutically acceptable carrier.