Sulfonamide derivative or pharmaceutically acceptable acid addition salt thereof

Patent metadata

Field	Value
Publication number	US-9815787-B2
Application number	US-201415103085-A
Country	US
Kind code	B2
Filing date	Dec 12, 2014
Priority date	Dec 12, 2013
Publication date	Nov 14, 2017
Grant date	Nov 14, 2017

Abstract

The present invention aims to provide a novel low-molecular-weight compound having an orexin agonist activity, which is expected to be useful as a superior agent for the treatment or prophylaxis of narcolepsy. The present invention provides a compound showing superior orexin agonist activity which is represented by the formula (I)

wherein each symbol is as defined in the DESCRIPTION, and a pharmaceutically acceptable acid addition salt thereof, as well as an orexin agonist containing the compound or a pharmaceutically acceptable acid addition salt thereof.

First claim

The invention claimed is:

1. A compound represented by the formula (I)

wherein
R 1 is a hydrogen atom, alkyl having 1 to 4 carbon atoms or halogen,
R 2 is a hydrogen atom, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, halogen, —OH, —NR 2a R 2b (wherein R 2a is a hydrogen atom, alkyl having 1 to 6 carbon atoms or cycloalkyl having 3 to 8 carbon atoms, R 2b is a hydrogen atom, alkyl having 1 to 6 carbon atoms or cycloalkyl having 3 to 8 carbon atoms), or the formula (a) or (b)

(wherein n′ is an integer of 1 to 4)
R 3 is a hydrogen atom or alkyl having 1 to 4 carbon atoms,
R 4 is a hydrogen atom or alkyl having 1 to 4 carbon atoms,
R 5 is aryl or heteroaryl (wherein aryl or heteroaryl is optionally substituted by optionally selected 1 to 4 R 6 ),
R 6 is a hydrogen atom, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, halogen, —CN, —CF 3 , —CH 2 F, —CHF 2 , —OCF 3 , —OH, —NO 2 or —NR 6a R 6b (wherein R 6a is a hydrogen atom, alkyl having 1 to 4 carbon atoms, —CH 2 CH 2 OMe or —CH 2 CH 2 OEt, R 6b is a hydrogen atom, alkyl having 1 to 4 carbon atoms, —CH 2 CH 2 OMe or —CH 2 CH 2 OEt),
W is the formula (II):

(wherein
R 7 is a hydrogen atom, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms or halogen,
R 8 is a hydrogen atom, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms or halogen,
X is —N═ or —CR 9 ═,
Y is —N═ or —CR 9 ═,
R 9 is a hydrogen atom, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, halogen, —OH, —NR 10 R 11 , —CH 2 OR 10 , —CF 3 , —OCF 3 , —CN, —C(O)OR 10 , —C(O)NR 10 R 11 , the formula (III) or (IV),

(wherein n is an integer of 1 to 4)
X and Y are —CR 9 ═, each R 9 may be the same or different,
R 11 is a hydrogen atom, alkyl having 1 to 4 carbon atoms, —CH 2 CF 3 , —CH 2 CH 2 OH or —CH 2 CH 2 OMe,
R 11 is a hydrogen atom, alkyl having 1 to 4 carbon atoms, —CH 2 CF 3 , —CH 2 CH 2 OH or —CH 2 CH 2 OMe,
or a pharmaceutically acceptable acid addition salt thereof.

2. The compound according to claim 1 , wherein
R 1 is a hydrogen atom or alkyl having 1 to 4 carbon atoms,
R 2 is a hydrogen atom, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms or halogen,
R 6 is alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, halogen, —CN, —CF 3 , —OH or —NR 6a R 6b (wherein R 6a is alkyl having 1 to 4 carbon atoms, R 6b is alkyl having 1 to 4 carbon atoms),
W is a compound of the formula (II):

(wherein
R 7 is a hydrogen atom, alkoxy having 1 to 4 carbon atoms or halogen,
R 8 is a hydrogen atom, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms or halogen,
X is —CR 9 ═ or —N═,
Y is —CR 9 ═ or —N═,
R 9 is a hydrogen atom, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, halogen, —OH, —NR 10 R 11 , —CH 2 OH, —C(O)OR 10 , —C(O)NR 10 R 11 or the formula (IV):

(wherein n is an integer of 1 to 4),
R 10 is a hydrogen atom, alkyl having 1 to 4 carbon atoms, —CH 2 CF 3 , —CH 2 CH 2 OH or —CH 2 CH 2 OMe, and
R 11 is a hydrogen atom, alkyl having 1 to 4 carbon atoms, —CH 2 CF 3 , —CH 2 CH 2 OH or —CH 2 CH 2 OMe,
or a pharmaceutically acceptable acid addition salt thereof.

Assignees

• Univ Tsukuba

Inventors

• Nagase Hiroshi
• Nagahara Takashi

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/20

  Hypnotics; Sedatives · CPC title

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• A61P25/18

  Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia · CPC title

• A61P3/00

  Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) · CPC title