Bicyclic aromatic sulfinyl derivatives
View Patent ↗The present invention provides compounds of the structure: wherein the constituent members are defined herein, including pharmaceutical compositions thereof and methods of treating diseases therewith.
1. A method of treating excessive sleepiness in a subject in need thereof comprising administering to said subject a therapeutically effective amount of a compound of formula (IV):
wherein
Ar is
wherein X is a bond, CH 2 , or O;
ring A optionally substituted with one to three groups selected from F, Cl, Br, I, OR 21 , OR 25 , NR 23 R 24 , NHOH, NO 2 , CN, C 1 -C 6 alkyl, and C(═O)R 22 ;
Y′ is C 1 -C 4 alkylene, wherein said alkylene group is optionally substituted with an R 20 group;
R 12 and R 13 at each occurrence are each independently selected from H, and C 1 -C 6 alkyl, wherein said alkyl group can optionally be substituted with one or two CN, OR 21 , O(CH 2 ) 1-4 OR 21 , C(═O)N(R 21 ) 2 , or pyridyl groups, or R 12 and R 13 , together with the nitrogen to which they are attached, form a pyrrolidinyl, piperidinyl, or piperazinyl ring, optionally substituted with OR 21 , C(═O)N(R 21 ) 2 , or C(═O)R 21 ;
R 20 at each occurrence is independently selected from F, Cl, Br, I, OR 21 , OR 25 , NR 23 R 24 , NHOH, NO 2 , CN, and CF 3 ;
R 21 at each occurrence is independently selected from H and C 1 -C 6 alkyl;
R 22 at each occurrence is independently selected from C 1 -C 6 alkyl, and phenyl;
R 23 and R 24 at each occurrence are each independently selected from H and C 1 -C 6 alkyl, or R 23 and R 24 , together with the nitrogen to which they are attached, form a 5-6 membered heterocycloalkyl;
R 25 at each occurrence is independently the residue of an amino acid after the hydroxyl group of the carboxyl group is removed;
or a stereoisomeric form, mixture of stereoisomeric forms or pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein X is a bond, Y′ is CH 2 , or CH 2 CH 2 , and R 12 and R 13 is H, C 1 -C 4 alkyl, optionally substituted with a CN, OR 21 , O(CH 2 ) 1-4 OR 21 group; or R 12 and R 13 , together with the nitrogen to which they are attached, form a pyrrolidinyl, piperidinyl, or piperazinyl ring, optionally substituted with OR 21 , C(═O)N(R 21 ) 2 , or C(═O)R 21 group.
3. The method of claim 1 , wherein X is CH 2 , Y′ is CH 2 , and R 12 and R 13 is H or C 1 -C 4 alkyl, or R 12 and R 13 , together with the nitrogen to which they are attached, form a pyrrolidinyl ring.
4. The method of claim 1 , wherein X is O, Y′ is CH 2 , and R 12 and R 13 is H or C 1 -C 4 alkyl, optionally substituted with a pyridyl group; or R 12 and R 13 , together with the nitrogen to which they are attached, form a pyrrolidinyl ring.
5. The method of claim 1 wherein the compound is selected from the following table:
Example
Structure
10
11
12
14
15
16
19
26
28
29
30
64
66
69
71
72
73
75
80
82
83
or a stereoisomeric form, mixture of stereoisomeric forms or pharmaceutically acceptable salt thereof.
6. The method of claim 5 , wherein the excessive sleepiness is associated with narcolepsy, obstructive sleep apnea or shift work disorder.