Described herein are small molecule splicing modulator compounds that modulate splicing of mRNA, such as pre-mRNA, encoded by genes, and methods of use of the small molecule splicing modulator compounds for modulating splicing and treating diseases and conditions.

The present invention is relates to a compound of formula (I),

##STR00001##

wherein
X.sup.1, X.sup.2 and X.sup.3 are, independently of each other, N or CH; with the proviso that at least two of X.sup.1, X.sup.2 and X.sup.3 are N;
Y is N or CH;
R.sup.1 and R.sup.2 are independently of each other (iii) a morpholinyl of formula (II)

##STR00002##

wherein the arrow denotes the bond in formula (I); and
wherein R.sup.3 and R.sup.4 are independently of each other H, C.sub.1-C.sub.3alkyl optionally substituted with one or two OH, C.sub.1-C.sub.2fluoroalkyl, C.sub.1-C.sub.2alkoxy, C.sub.1-C.sub.2alkoxyC.sub.1-C.sub.3alkyl, CN, or C(O)O—C.sub.1-C.sub.2alkyl; or R.sup.3 and R.sup.4 form together a bivalent residue —R.sup.5R.sup.6— selected from C.sub.1-C.sub.3alkylene optionally substituted with 1 to 4 F, —CH.sub.2—O—CH.sub.2—, —CH.sub.2—NH—CH.sub.2—, or any of the structures

##STR00003##

wherein the arrows denote the bonds in formula (II); or (iv) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally substituted by 1 to 3 R.sup.7; wherein R.sup.7 is independently at each occurrence C.sub.1-C.sub.3alkyl optionally substituted with one or two OH, C.sub.1-C.sub.2fluoroalkyl, C.sub.1-C.sub.2alkoxyC.sub.1-C.sub.3alkyl, C.sub.3-C.sub.6cycloalkyl; or two R.sup.7 substituents form together a bivalent residue —R.sup.8R.sup.9— selected from C.sub.1-C.sub.3alkylene optionally substituted with 1 to 4 F, —CH.sub.2—O—CH.sub.2— or —O—CH.sub.2CH.sub.2—O—;
with the proviso that at least one of R.sup.1 and R.sup.2 is a morpholinyl of formula II;
and prodrugs, metabolites, tautomers, solvates and pharmaceutically acceptable salts thereof, for use in the prevention or treatment of a neurological disorder in a subject.

The present invention is relates to a compound of formula (I),

##STR00001##

wherein
X.sup.1, X.sup.2 and X.sup.3 are, independently of each other, N or CH; with the proviso that at least two of X.sup.1, X.sup.2 and X.sup.3 are N;
Y is N or CH;
R.sup.1 and R.sup.2 are independently of each other (iii) a morpholinyl of formula (II)

##STR00002##

wherein the arrow denotes the bond in formula (I); and
wherein R.sup.3 and R.sup.4 are independently of each other H, C.sub.1-C.sub.3alkyl optionally substituted with one or two OH, C.sub.1-C.sub.2fluoroalkyl, C.sub.1-C.sub.2alkoxy, C.sub.1-C.sub.2alkoxyC.sub.1-C.sub.3alkyl, CN, or C(O)O—C.sub.1-C.sub.2alkyl; or R.sup.3 and R.sup.4 form together a bivalent residue —R.sup.5R.sup.6— selected from C.sub.1-C.sub.3alkylene optionally substituted with 1 to 4 F, —CH.sub.2—O—CH.sub.2—, —CH.sub.2—NH—CH.sub.2—, or any of the structures

##STR00003##

wherein the arrows denote the bonds in formula (II); or (iv) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally substituted by 1 to 3 R.sup.7; wherein R.sup.7 is independently at each occurrence C.sub.1-C.sub.3alkyl optionally substituted with one or two OH, C.sub.1-C.sub.2fluoroalkyl, C.sub.1-C.sub.2alkoxyC.sub.1-C.sub.3alkyl, C.sub.3-C.sub.6cycloalkyl; or two R.sup.7 substituents form together a bivalent residue —R.sup.8R.sup.9— selected from C.sub.1-C.sub.3alkylene optionally substituted with 1 to 4 F, —CH.sub.2—O—CH.sub.2— or —O—CH.sub.2CH.sub.2—O—;
with the proviso that at least one of R.sup.1 and R.sup.2 is a morpholinyl of formula II;
and prodrugs, metabolites, tautomers, solvates and pharmaceutically acceptable salts thereof, for use in the prevention or treatment of a neurological disorder in a subject.

This invention relates to compounds that are agonists of the muscarinic M.sub.1 and/or M.sub.4 receptor and which are useful in the treatment of diseases mediated by the muscarinic M.sub.1 and M.sub.4 receptors. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula ##STR00001##
where X.sup.1; X.sup.2; X.sup.3; X.sup.4; R.sup.1 R.sup.2 and R.sup.4 are as defined herein.

This invention relates to compounds that are agonists of the muscarinic M.sub.1 and/or M.sub.4 receptor and which are useful in the treatment of diseases mediated by the muscarinic M.sub.1 and M.sub.4 receptors. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula ##STR00001##
where X.sup.1; X.sup.2; X.sup.3; X.sup.4; R.sup.1 R.sup.2 and R.sup.4 are as defined herein.

The invention provides compounds of formula (I):

##STR00001##

or pharmaceutically-acceptable salts thereof, that are inhibitors of Janus kinases and release an active metabolite in vivo. The invention also provides pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat inflammatory skin diseases and other diseases.

Described herein are small molecule splicing modulator compounds that modulate splicing of mRNA, such as pre-mRNA, encoded by genes, and methods of use of the small molecule splicing modulator compounds for modulating splicing and treating diseases and conditions.

Described herein are small molecule splicing modulator compounds that modulate splicing of mRNA, such as pre-mRNA, encoded by genes, and methods of use of the small molecule splicing modulator compounds for modulating splicing and treating diseases and conditions.

This invention relates to compounds that are agonists of the muscarinic M.sub.1 and/or M.sub.4 receptor and which are useful in the treatment of diseases mediated by the muscarinic M.sub.1 and M.sub.4 receptors. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula ##STR00001##
where Y, R.sup.1, R.sup.2 and R.sup.4 are as defined herein.

This invention relates to compounds that are agonists of the muscarinic M.sub.1 and/or M.sub.4 receptor and which are useful in the treatment of diseases mediated by the muscarinic M.sub.1 and M.sub.4 receptors. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula ##STR00001##
where Y, R.sup.1, R.sup.2 and R.sup.4 are as defined herein.