Sulfonamide derivative or pharmaceutically acceptable acid addition salt thereof
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.
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.