2-alkylbenzoxazole carboxamides as 5HT3 modulators
View Patent ↗Compounds of formulae I and II: are disclosed as 5-HT 3 inhibitors. Those compounds are useful in treating CINV, IBS-D and other diseases and conditions.
1. A method of treating irritable bowel syndrome, emesis, or post-operative nausea or vomiting, which comprises administering to a patient in need of such treatment a therapeutically effective amount of a compound of formula
wherein
R 1 , R 2 and R 3 are independently selected from the group consisting of hydrogen, halogen, amino, alkylamino, dialkylamino, acylamino, morpholinyl, —O-loweralkyl, hydroxy, loweralkyl, fluoroloweralkyl, —O-lowerfluoroalkyl, methylenedioxy, ethylenedioxy, alkoxy-loweralkyl and hydroxyloweralkyl;
R 4 is a residue selected from the group consisting of:
(i) a saturated nitrogen heterocycle or methyl-substituted saturated nitrogen heterocycle, in which said nitrogen is tertiary, said heterocycle containing at least one 5 or 6-membered ring; and
(ii) an imidazolylalkyl residue wherein the imidazole of said imidazolylalkyl is optionally substituted with up to three groups chosen from halogen, (C 1 -C 4 )alkyl, substituted (C 1 -C 4 )alkyl and NH 2 ; and
R 10 is selected from the group consisting of
(i) hydrogen;
(ii) (C 1 -C 10 )alkyl;
(iii) substituted (C 1 -C 10 )alkyl;
(iv) saturated C-attached heterocyclyl; and
(v) substituted, saturated C-attached heterocyclyl.
2. A method according to claim 1 wherein said disorder is irritable bowel syndrome.
3. A method according to claim 1 for treating emesis.
4. A method according to claim 1 for treating post-operative nausea or vomiting.