Substituted benzamides

Patent metadata

Field	Value
Publication number	US-9452980-B2
Application number	US-96961310-A
Country	US
Kind code	B2
Filing date	Dec 16, 2010
Priority date	Dec 22, 2009
Publication date	Sep 27, 2016
Grant date	Sep 27, 2016

Abstract

The invention relates to compounds of formula

wherein R, R 1 , R 2 , X, and Y are as defined herein and to a pharmaceutically suitable acid addition salt thereof.

Compounds of formula I have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1. The compounds can be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

First claim

The invention claimed is:

1. A compound selected from the group consisting of
(RS)-6-Pyrazol-1-yl-N-(4-pyrrolidin-3-yl-phenyl)-nicotinamide;
or a pharmaceutically suitable acid addition salt thereof.

2. A compound selected from the group consisting of
(RS)—N-(4-Pyrrolidin-3-yl-phenyl)-6-(2,2,2-trifluoro-ethoxy)-nicotinamide
or a pharmaceutically suitable acid addition salt thereof.

3. A compound selected from the group consisting of
(RS)-5-Trifluoromethyl-pyridine-2-carboxylic acid (4-piperidin-3-yl-phenyl)-amide;
(RS)-5-Trifluoromethyl-pyridine-2-carboxylic acid (4-pyrrolidin-3-yl-phenyl)-amide; and
(RS)-5-Trifluoromethyl-pyridine-2-carboxylic acid (4-morpholin-2-yl-phenyl)-amide; or a pharmaceutically suitable acid addition salt thereof.

4. A compound wherein said compound is (RS)—N-(4-(Piperidin-3-yl)phenyl)-6-(2,2,2-trifluoroethoxy)nicotinamide
or a pharmaceutically suitable acid addition salt thereof.

5. A compound selected from the group consisting of
(RS)—N-(4-(Piperidin-3-yl)phenyl)-5-(2,2,2-trifluoroethoxy)picolinamide; and
(RS)-2-(4-(6-cyanonicotinamido)phenyl)morpholin-4-ium chloride;
or a pharmaceutically suitable acid addition salt thereof.

6. A compound selected from the group consisting of
(R)—N-(4-(Pyrrolidin-3-yl)phenyl)-6-(2,2,2-trifluoroethoxy)nicotinamide; and
(S)—N-(4-(Pyrrolidin-3-yl)phenyl)-6-(2,2,2-trifluoroethoxy)nicotinamide;
or a pharmaceutically suitable acid addition salt thereof.

7. A compound selected from the group consisting of
(RS)—N-(4-(Morpholin-2-yl)phenyl)-6-(2,2,2-trifluoroethoxy)nicotinamide; and
(R)—N-(4-(Piperidin-3-yl)phenyl)-6-(2,2,2-trifluoroethoxy)nicotinamide;
or a pharmaceutically suitable acid addition salt thereof.

8. A compound selected from the group consisting of
(S)—N-(4-(Piperidin-3-yl)phenyl)-6-(2,2,2-trifluoroethoxy)nicotinamide;
(RS)—N-(4-(Morpholin-2-yl)phenyl)-2-phenylthiazole-5-carboxamide; and
(RS)—N-(4-(Morpholin-2-yl)phenyl)-2-phenylthiazole-4-carboxamide;
or a pharmaceutically suitable acid addition salt thereof.

9. A compound selected from the group consisting of
(S)-5-(Methylthio)-N-(4-(piperidin-3-yl)phenyl)pyrazine-2-carboxamide; and
(R)—N-(4-(Piperidin-3-yl)phenyl)-6-(trifluoromethyl)nicotinamide;
or a pharmaceutically suitable acid addition salt thereof.

10. A compound selected from the group consisting of
(R)—N-(4-(Morpholin-2-yl)phenyl)-6-(2,2,2-trifluoroethoxy)nicotinamide;
(S)—N-(4-(Morpholin-2-yl)phenyl)-6-(2,2,2-trifluoroethoxy)nicotinamide; and
(RS)—N-(4-(Morpholin-2-yl)phenyl)-6-(pyrrolidin-1-yl)nicotinamide;
or a pharmaceutically suitable acid addition salt thereof.

11. A compound selected from the group consisting of
N-(4-(Morpholin-2-yl)phenyl)-2-(trifluoromethyl)isonicotinamide;
(R)—N-(4-(Morpholin-2-yl)phenyl)-6-(trifluoromethyl)nicotinamide;
(S)—N-(4-(Morpholin-2-yl)phenyl)-6-(trifluoromethyl)nicotinamide;
(RS)—N-(4-(Morpholin-2-yl)phenyl)-2-(pyrazin-2-yl)thiazole-4-carboxamide;
(S)—N-(4-(Piperidin-3-yl)phenyl)-6-propylnicotinamide; and
(S)-6-Ethyl-N-(4-(piperidin-3-yl)phenyl)nicotinamide;
or a pharmaceutically suitable acid addition salt thereof.

12. A compound wherein said compound is (RS)—N-(4-(Morpholin-2-yl)phenyl)-1-phenyl-1H-pyrazole-3-carboxamide
or a pharmaceutically suitable acid addition salt thereof.

13. The compound of claim 11 wherein said compound is N-(4-(Morpholin-2-yl)phenyl)-2-(trifluoromethyl)isonicotinamide or a pharmaceutically suitable acid addition salt thereof.

14. The compound of claim 13 wherein said compound is (RS)—N-(4-(Morpholin-2-yl)phenyl)-2-(trifluoromethyl)isonicotinamide or a pharmaceutically suitable acid addition salt thereof.

Assignees

• Groebke Zbinden Katrin
• Norcross Roger
• Pflieger Philippe
• Hoffmann La Roche

Inventors

• Groebke Zbinden Katrin
• Norcross Roger
• Pflieger Philippe

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title